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Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Osteoporosis (OP) is a systemic skeletal disease, the development of which is co-regulated by multiple tissues throughout the body. As interdependent parts of the locomotor system, muscle and bone are in cross-talk and work together to maintain the dynamic balance of the musculoskeletal system. Previous studies viewed the musculoskeletal system as a mechanical structure and focused on the biomechanical interactions between the two. In recent years, the biochemical crosstalk between bone and skeletal muscle as endocrine organs has been emphasized. In particular, skeletal muscle regulates bone metabolism and OP development by secreting myokines. A comprehensive summary and update of the findings related to the regulation of bone metabolism by myokines in muscle-bone biochemical crosstalk is presented. In this review, we will classify myokines according to their influence on bone formation, bone resorption, and both, in order to gain insights into the pathogenesis of OP and to explore new therapeutic approaches. Furthermore, we also summarize the current myogenic factors or possible myogenic factors with potential research value on bone metabolism, hopefully providing directions for the research related to the musculoskeletal cross-talk and the regulation of bone metabolism by myogenic factors.

Shao-Long Chen,1 Yao-Jie Shen,2 Guo-Zhi Chen1 1Department of Infectious Disease Control and Prevention, Yueqing Center for Disease Control and Prevention, Wenzhou, 325600, People’s Republic of China; 2Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Shao-Long Chen, Yueqing Center for Disease Control and Prevention, Wenzhou, 325600, People’s Republic of China, Email chenshaolong@zjsru.edu.cnPurpose: Worldwide, chronic hepatitis B virus (CHB) infection is a public health concern, ultimately leading to liver cirrhosis and hepatocellular carcinoma. Currently, patients with CHB can be treated using polyethylene glycol (PEG)ylated interferon (PEG-IFN) antiviral therapy, which has both immune modulatory and antiviral properties. This study aimed to reveal the mechanism underlying the effect of PEG-IFN therapy, to rationally optimize this therapeutic option.Patients and Methods: Ten patients with CHB who were positive for the hepatitis B virus e antigen (HBeAg) and were receiving PEG-IFN treatment were enrolled. Clinical and virological parameters were monitored during 48 weeks of treatment. In addition, peripheral blood mononuclear cells (PBMCs) were collected from the 10 patients at 0, 24, and 36 weeks. RNA sequencing technology was used to analyze the RNA expression profile in the PBMC samples.Results: Following PEG-IFN treatment, we identified 217 differentially expressed genes (DEGs), most of which were upregulated. Gene ontology enrichment analysis of the DEGs revealed that they were enriched in 29 clusters, mainly associated with “antiviral defense”, “innate immunity”, “immunity”, “defense response to virus”, “response to virus”, “type I interferon signaling pathway”, “negative regulation of viral genome replication”, “innate immune response”, and “RNA-binding”.Conclusion: After PEG-IFN treatment, a certain mRNA expression profile was observed in patients with CHB, providing further mechanistic insights into the antiviral effect of this therapy.Keywords: Chronic infection, Hepatitis B, PEGylated interferon, RNA sequencing

Jun Wang,1 Yuan Liu,2 Guo-zhen Jin3 1Department of Cardiology, Hongze District People’s Hospital, Huaian, 223100, People’s Republic of China; 2Community Health Service Center of Huaihai Road, Nanjing, 210002, People’s Republic of China; 3Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of ChinaCorrespondence: Guo-zhen Jin, Email wjjinguozhen@126.comObjective: The success rate of polyvinyl alcohol (PAV) granules in the treatment of coronary artery perforation (CAP) was investigated to determine their safety and efficacy.Methods: Forty patients with II and III coronary artery perforations during percutaneous coronary intervention were divided into two groups. One group was only occluded by low pressure balloons (balloon occlusion group), and the other one was occluded with PVA granules during low-pressure balloon dilatation (PVA granules embolization group). Retrospective analysis of clinical data was used to compare the success rate and safety of various methods.Results: The balloon embolization group had 16 cases (88.9%) of coronary perforation type II and 2 cases (11.1%) of coronary perforation type III. The PVA granules embolization group had 20 cases (90.9%) of coronary perforation type II and 2 cases (9.1%) of coronary perforation type III. Of the 18 patients in the balloon occlusion group, 13 were immediately occluded, with a success rate of 72.2%, while the remaining 5 required embolization or covered stents. 6 of the 18 patients had pericardial effusion, and two of them underwent pericardiocentesis. Among the 22 patients in the PVA granules embolization group, 21 were immediately blocked, with a 95.5% success rate, while the other was occluded by a covered stent. The results revealed that the success rate of transcatheter closure in the PVA granules embolization group was significantly higher than that in the balloon embolization group, and the risk of pericardial effusion and pericardiocentesis in the PVA granules embolization group was significantly lower than that in the balloon embolization group.Conclusion: In comparison to the simple use of low-pressure balloon occlusion, the use of PAV granules in the treatment of II, III coronary artery perforation has a high success rate and safety, and is a viable method for treating coronary artery perforation.Keywords: percutaneous coronary intervention, coronary artery perforation, polyvinyl alcohol granules

Hong-Mei Shu,1,* Chang-Qing Lin,1 Bei He,1 Wang Wang,1 Ling Wang,1 Ting Wu,1 Hai-Juan He,1 Hui-Juan Wang,1 He-Ping Zhou,2 Guo-Zheng Ding1,* 1Department of Pulmonary and Critical Care Medicine, Anqing Municipal Hospital, Anhui, People’s Republic of China; 2Neurosurgery Department, Anqing Municipal Hospital, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Mei Shu, Email shuxin501@163.comBackground: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The “ConsensusClusterPlus” package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT – PCR to detect the expression levels of eight genes in COPD patient and normal.Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.Keywords: chronic obstructive pulmonary disease, pyroptosis, gene, biomarkers, immune Infiltration

Jane Kasozi Namagga,1 Godfrey Zari Rukundo,2 Vincent Batwala,3 Vallence Niyonzima,1 Hanifah Nantongo,1 Grace Nambozi1 1Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 2Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of Community Health, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Jane Kasozi Namagga, Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda, Tel +256 772 461623, Email jkasozi@must.ac.ugIntroduction: HIV-associated neurocognitive disorders (HAND) are becoming a significant public health concern in the continuum of human immune virus (HIV) treatment. These disorders range from subtle cognitive impairments to severe dementia. Despite many early-stage HAND cases being asymptomatic, healthcare workers (HCWs) rarely perform routine neurocognitive assessments. This leads to a high number of unrecognized cases and increases the risk of HAND among people living with HIV (PLWH).Material and Methods: We aimed to explore HCWs’ perspectives on integrating the International HIV Dementia Scale (IHDS) into routine care for screening HAND at The AIDS Support Organization (TASO) centres in central and southwestern Uganda.Results: We conducted five focus group discussions with 37 HCWs from five TASO centres. Thematic analysis revealed eight key theme: 1) Impaired brain function, 2) Changes in activities of daily living, 3) Promotion of quality care perspectives, 4) Tool applicable and user-friendly, 5) Client increased self-awareness and self-confidence, 6) Integration of IHDS into routine HIV care, 7) Uncertainty about IHDS use, and 8) Continuous training for HCWs.Conclusion: As PLWH enjoy longer and healthier lives, their risk for HAND increases, potentially affecting their quality of life. The use of the IHDS has raised awareness among HCWs and improved decision-making through cognitive assessments, emphasizing it value in PLWH. We recommend a prospective study to assess the long-term outcomes and efficacy of increased HAND screening. Furthermore, integrating a HAND screening module into the consolidated HIV guidelines is recommended to enhance its relevance.Keywords: healthcare workers, HIV associated neurocognitive disorders, international HIV dementia scale, screening

Objetivos: Avaliar os desfechos clínicos de pacientes com Linfoma B de Alto Grau em uma coorte retrospectiva, comparando a sobrevida entre diferentes protocolos de tratamento. Secundariamente, investigar a influência das translocações BCL2 e BCL6 nos desfechos. Material e métodos: Estudo de coorte retrospectiva incluindo pacientes diagnosticados com Linfoma B de Alto Grau, tratados no Hospital de Câncer de Barretos entre 17 de fevereiro de 2020 e 22 de dezembro de 2023. Analisamos características clínico-patológicas, protocolos de tratamento e desfechos. A sobrevida global e livre de progressão foram estimadas pelo método de Kaplan-Meier e comparadas pelo teste de log-rank. Resultados: Foram incluídos 29 pacientes, dos quais três não receberam tratamento. A idade mediana foi de 51 anos (mínima 22, máxima 83), com distribuição equilibrada entre os sexos (15 masculinos, 14 femininos). A maioria dos pacientes (72,4%) apresentava-se em estágio avançado da doença. Entre os pacientes tratados, o protocolo R-CHOP (Rituximabe, Ciclofosfamida, Doxorrubicina, Vincristina e Prednisona) foi o mais utilizado (38,5%), seguido pelo R-DAEPOCH (Rituximabe, Dose-Ajustada de Etoposídeo, Ciclofosfamida e Doxorrubicina, Prednisona e Vincristina) (30,8%) e outros protocolos (30,8%). A profilaxia do sistema nervoso central foi realizada em 65,5% dos pacientes. Observamos taxa de resposta completa de 37,9%, refratariedade de 41,4% e mortalidade de 55,2%. As análises de sobrevida demonstraram uma sobrevida global em 48 meses de 70% para R-DAEPOCH versus 14,3% para R-CHOP (p = 0,17). A sobrevida livre de progressão não foi relatada separadamente, pois apenas um paciente apresentou recidiva antes do óbito, resultando em taxas idênticas às da sobrevida global. Identificamos 24,1% de casos com translocação de BCL2 e 6,9% com translocação de BCL6. Não houve diferença estatisticamente significativa na sobrevida global (p = 0,51) entre pacientes com ou sem estas translocações. Discussão: Nossos resultados corroboram a natureza agressiva dos Linfomas B de Alto Grau, com altas taxas de refratariedade (41,4%) e mortalidade (55,2%). A maioria dos pacientes (72,4%) apresentava-se em estágio avançado, possivelmente refletindo atrasos no diagnóstico, comuns em serviços públicos de saúde. Apesar do viés de seleção do tratamento baseado em performance status, idade e comorbidades, observamos uma tendência de superioridade do R-DAEPOCH sobre o R-CHOP (sobrevida global em 2 anos: 70,0% vs 14,3%, p = 0,17). Embora não estatisticamente significativa, esta tendência alinha-se com estudos prévios. A ausência de diferença significativa nos desfechos entre linfomas com ou sem translocações adicionais (p = 0,51) sugere que outros fatores podem influenciar o prognóstico, mas deve ser interpretada com cautela devido ao tamanho amostral limitado. Conclusão: O protocolo R-DAEPOCH mostrou tendência de melhores desfechos em Linfomas B de Alto Grau. Contudo, a agressividade da doença e o diagnóstico tardio em serviços públicos ainda resultam em altas taxas de refratariedade e mortalidade. É essencial buscar estratégias para melhorar o prognóstico, incluindo diagnóstico precoce e otimização do tratamento.

Introduction: Solid organ transplantation (SOT) is an effective treatment modality for children and young adults with end-stage organ failure with 5-year overall survival ranging from 25 to 95% depending on the transplanted organ. Patients subsequently require lifelong immunossupression to maintain graft health and limit the risk of graft rejection. Commonly used immunosuppressants to inhibit organ recipient T-lymphocyte function include calcineurin inhibitors (CNI), mTOR inhibitors, thiopurines, and antimetabolites. Most cases of monomorphic Post-Transplantation Lymphoproliferative Disorders (m-PTLD) are related to the Epstein Barr virus (EBV) and occur in patients who were EBV seronegative before the transplant. Objective: Our aim is to assess the overall survival in patients diagnosed with monomorphic Post-Transplantation Lymphoproliferative Disorders after SOT. Methods: We present retrospective data on 46 pediatric patients diagnosed with monomorphic Post-Transplantation Lymphoproliferative Disorders with Non-Hodgkin Lymphoma (NHL) after SOT in our Institution between 2001 and 2024. Results: Twenty four of the 46 were male, and 22 were female, and mean age at the time of diagnosis of PTLD was 8 years (age range, 11 months to 17 years). PTLD was diagnosed at a median time of 36 months after the organ transplant, with a significantly shorter interval in liver (20/46), 31 months, versus heart (15/46) or kidney (11/46) graft recipients (48- and 42-months years, respectively p < 0,05). Most common histopathology subtypes were Burkitt in 20/46 (44%), Diffuse Large B-cell lymphoma (DLBCL) in 19/46 (41%) and other NHL in 7/46 (15%). Most common sites were abdominal (17/46), followed by cervical and axillary lymph nodes (12/46). Murphy staging system revealed: Stage I (5/46 - 11%), Stage II (5/46 - 11%) and Stage III (33/46 -72%). Stage IV diseases with bone marrow (1/46 – 2%) and/or Central nervous system Involvement (CNS) (2/46 - 4%). The treatment carried out was reduction of immunosuppression and rituximab in 18 patients, with chemotherapy, rituximab and reduction of immunosuppression in 28 patients. In one relapse there was a need for bone marrow transplantation. No differences in outcome were observed between Early (22/46) and late-onset (24/46) PTLD and EBV-positive (14/46) or EBV-negative (25/46) PTLD, respectively. The 5-year overall and event-free survival were 91% and 83%, respectively. Conclusion: The outcome of m-PTLD has clearly improved as a result of the introduction of more uniform treatment protocols and improved supportive care, instaging and response monitoring. The majority of had a good response with chemotherapy and/or rituximab.

Existem poucos trabalhos que analisam a associação entre Mucosite Oral (MO) e desequilíbrio nutricional em crianças durante o Transplante de Células Hematopoiéticas (TCH). O objetivo deste trabalho foi comparar os fatores de risco para a MO e o desequilíbrio nutricional durante o TCH em pacientes pediátricos com Doenças não Malignas (DNM) e Doenças Malignas (DM). Foram selecionados 132 prontuários de pacientes pediátricos com idades entre 0 e 18 anos, que foram submetidos a TCH, tratados no Centro de Transplante de Medula Óssea do Hospital Israelita Albert Einstein, entre os anos de 2012 e 2019. Foram coletados dados, incluindo dentre outras informações: idade, sexo, doença primária, tipo de transplante, regime de condicionamento, profilaxia para Doença do Enxerto Contra o Hospedeiro (DECH), toxicidade gastrointestinal, gradação de mucosite oral, porcentagem de perda e ganho de peso corporal, reposição nutricional e Sobrevida Global (SG). Os dados foram comparados entre pacientes com DNM (n = 70) e DM (n = 62). Observou-se que a MO teve gravidade semelhante entre os dois grupos. O principal fator de risco no grupo DNM foi o regime de condicionamento com bussulfano, enquanto no grupo DM foi a profilaxia para DECH com ciclosporina e metotrexato. A MO não teve impacto na perda ou ganho de peso corporal em nenhum dos grupos. No grupo DNM, o ganho de peso corporal devido à sobrecarga de fluidos foi mais pronunciado e associado a uma faixa etária menor. A OS foi semelhante entre os grupos e não foi afetada pela MO. Conclui-se que o padrão de MO foi semelhante em pacientes pediátricos com ou sem DM, mas os fatores que determinaram essas lesões orais foram diferentes. Houve disparidades nas mudanças de peso corporal entre os dois grupos, e essas mudanças não foram associadas à MO.

ABSTRACT This study aimed to determine the prevalence of Eimeria spp., including the recently described Eimeria species Eimeria lata, Eimeria nagambie, and Eimeria zaria, on commercial broiler chicken farms (CBCFs) in the western region of the state of Santa Catarina, and to correlate their prevalence with the anticoccidial programs. Ninety-six fecal samples corresponding to 96 commercial broiler farms were examined by microscopic screening and genus-specific PCR (ITS-1 gene). All positive samples were subjected to genus-specific nested PCR (18S rRNA gene), followed by next-generation sequencing to identify the Eimeria species, and new Eimeria operational taxonomic units. Eimeria spp. were identified in 80.2% (77/96) of the samples. Next-generation sequencing revealed the following order of prevalence: Eimeria acervulina (70/77; 90.9%), Eimeria maxima (65/77; 84.4%), Eimeria mitis/mivati (17/77; 22.1%), and Eimeria praecox (37/77; 48.1%). Eimeria spp. were identified on 100% (62/62) and 44% (15/34) of the CBCFs employing treatment with salinomycin and nicarbazin, respectively. In conclusion, we observed a greater prevalence of Eimeria acervulina and Eimeria maxima; a lower prevalence of Eimeria mitis and Eimeria praecox; and the absence of Eimeria brunetti, Eimeria lata, Eimeria nagambie, Eimeria necatrix/tenella, and Eimeria zaria. There was lower positivity for Eimeria spp. on CBCFs employing treatment with nicarbazin.

Li-Hua Yang,1,&ast; Guo-Zhou Wang,1,&ast; Chao Gao2 1Department of Breast Tumor Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, People’s Republic of China; 2Department of General Practitioner, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Gao, Department of General Practitioner, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, 435000, People’s Republic of China, Email gaochaotongxue1987@163.comBackground: The survival rate for triple-negative breast cancer (TNBC) is very low due to its advanced metastatic and aggressive nature, and there is no specific target to improve the survival rate. The expression and clinical signature of neuronal-specific septin-3 (Septin3, SEPT3) in TNBC remain undetermined.Methods: SEPT3 differential expression in TNBC was detected with the use of bioinformatic approaches based on TCGA and GEO database, which was verified with immunohistochemistry in TNBC tissues. Next, the effect of SEPT3 on survival and the association between SEPT3 expression and clinical characteristics were assessed for TNBC patients. We performed Cox analysis to evaluate whether SEPT3 is an independent predictor for TNBC patients.Results: SEPT3 was identified as a key differentially expressed gene. SEPT3 was observed to be elevated in 112 TNBC significantly. Increased expression of SEPT3 contributed to an unfavorable prognosis in patients with TNBC. Additionally, SEPT3 was associated with several factors including TNM stage, lymph node metastasis, Ki67 level and histological grade. SEPT3 was determined to be an independent risk factor for TNBC patients through Cox regression analysis.Conclusion: This study demonstrated that SEPT3 could be a potential disease marker for TNBC patients by bioinformatics analysis and validation in clinical samples.Keywords: triple-negative breast cancer, STEP3, prognosis, biomarker

Judith Owokuhaisa,1 Catherine N Abaasa,2 Rose Muhindo,3 Pius Musinguzi,4 Godfrey Zari Rukundo5 1Faculty of Medicine, Department of Physiotherapy, Mbarara University of Science and Technology, Mbarara, Uganda; 2Faculty of Medicine, Department of Medical Laboratory Sciences, Mbarara University of Science and Technology, Mbarara, Uganda; 3Faculty of Medicine, Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 4Faculty of Medicine, Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 5Faculty of Medicine, Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Judith Owokuhaisa, Email jowokuhaisa@must.ac.ugBackground: Screening for kidney disease (KD) among high-risk patients (patients with hypertension or diabetes) allows early diagnosis, intervention and delayed progression of the disease. In low- and middle-income countries (LMIC), KD screening is still sub-optimal. This study explored the healthcare providers’ perceived barriers and facilitators to KD screening among older adults with hypertension and diabetes in Mbarara southwestern Uganda.Methods: This was a descriptive qualitative study among healthcare providers caring for older adults with diabetes mellitus and hypertension at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. In-depth interviews were conducted using a semi-structured interview guide. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed to develop themes of barriers and facilitators.Results: We conducted 30 in-depth interviews among healthcare providers. Barriers to screening for kidney disease included patient related factors according to healthcare providers (financial hardships, poor health seeking behavior, limited knowledge and awareness), healthcare factors (work overload, ineffective patient healthcare provider communication) and system/policy related factors (lack of laboratory supplies, lack of guidelines and poor medical record keeping and documentation). With respect to facilitators, we found formation of peer support groups, effective team, and continuous medical education (CME).Conclusion: Healthcare providers encounter substantial but modifiable barriers in screening older adults for KD. The identification of barriers and facilitators in timely KD detection gives us an outlook of the problem in Uganda and leads for proposals of action. Interventions that address these barriers and promote facilitators may improve the healthcare provider’s effectiveness and capacity to care including screening for patients at risk of KD.Keywords: healthcare providers, barriers, facilitators, screening, kidney disease, hypertension, diabetes, older, adults

Mohammed Alnuhait,1 Nada Falah Alqurashi,1 Ghodwah Zubair Abdullatif,1 Manar Sami Maash,1 Refal Fagieha,1 Haneen Alshareef,2 Foud O Bahamdain,2 Waad Alghamdi,3 Abdullah A Alhifany1 1Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 2Clinical Pharmacy Department, King Abdullah Medical City, Makkah, Saudi Arabia; 3College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Mohammed Alnuhait, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia, Email manuhait@uqu.edu.saIntroduction: Entrepreneurship has recently become a focus in community development, innovation, and economic growth, including within pharmaceutical organizations. However, it remains a relatively new aspect of pharmacy education. For the effective incorporation of entrepreneurship in this field, a robust educational foundation is critical, one that emphasizes risk-taking, strategic planning, competitive spirit, and a sense of social responsibility. This study aims to evaluate Saudi pharmacists’ attitudes towards entrepreneurship in their practice.Methods: A cross-sectional survey design to assess the attitudes of pharmacists and pharmacy students in Saudi Arabia towards entrepreneurship. The study sample consisted of 302 individuals, selected through convenience sampling, all of whom were either licensed pharmacists or pharmacy students in Saudi Arabia. The survey was conducted electronically and disseminated online throughout the duration of January 2023, spanning a one-month period. The research sought to provide a deeper understanding of how entrepreneurship is perceived within the pharmacy field.Results: The study involved 302 pharmacists in Saudi Arabia, with the majority being pharmacy students and Doctor of Pharmacy holders. Over 60% of the participants worked for the government sector. Results showed a strong interest in entrepreneurship, with nearly 80% expressing interest and believing in the entrepreneurial potential of pharmacists. However, there was a knowledge gap, as only 52% were familiar with entrepreneurship concepts, and most had not taken entrepreneurship courses. More than half of the participants reported insufficient institutional support for entrepreneurship. Remarkably, only 1% had started a pharmaceutical business.Conclusion: In conclusion, this study emphasizes the interest in entrepreneurship among pharmacists, highlighting the need for raising familiarity and formal education in the field. Factors such as working in the government sector were associated with higher willingness to become entrepreneurs, while the lack of awareness and institutional support hindered the entrepreneurial mindset.Keywords: entrepreneurship, pharmacy, Saudi Arabia, pharmacists, mindsets

Zhe-Feng Zhao,1,&ast; Bing-Bing Liu,1,&ast; Jian-Nan Zhang,2,&ast; Ni Shi,3,&ast; Ping Zhang,1,&ast; Gang-Zhi Yang,4 Yu-Fu Cao,4 Long-He Tian,4 Cheng-Cai Qiu,5 Yang Gao6,7 1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Neurosurgery, People’s Hospital of Hegang City, Hegang, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, Traditional Chinese Medicine Hospital of Jixi City, Jixi, Heilongjiang, People’s Republic of China; 6Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 7Institute of Critical Care Medicine, The Sino Russian Medical Research Center of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhe-Feng Zhao, Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email know810512@163.com Yang Gao, Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email gaoyang0312@126.comObjective: In this study, we aimed to explore the demographic and clinical factors that could determine short- and long-term complete pain relief (CPR) in adult patients with primary trigeminal neuralgia (PTN) after microvascular decompression (MVD) to guide clinical practice.Methods: This single-center retrospective study included adult patients with PTN who underwent MVD as their initial neurosurgical procedure in the Department of Neurosurgery at the Second Affiliated Hospital of Harbin Medical University from January 2017 to December 2019 and completed a 3-year post-surgery follow-up. Demographic and clinical information was obtained from medical records. Pain relief of adult patients with PTN at various time points after sufficient decompression of trigeminal nerve (TN) during MVD was determined and classified by the patient’s subjective response and medications use. Pain relief of local patients was evaluated by outpatient follow-up at various time points, whereas that of local cases who could not return to outpatient or non-local cases was assessed through telephone or WeChat.Results: In univariate analysis, compression degree of TN and type of conflicting vessels constantly showed significant differences between the two groups at 3 months, 6 months, 1 year, 2 years, and 3 years after MVD. Compression degree of TN and type of conflicting vessels at various time points after MVD were always the related factors to CPR in logistic regression analysis, with the former having the greatest impact. The areas under the receiver operating characteristic (ROC) curve of CPR at various time points after MVD were 0.937, 0.874, 0.879, 0.864, and 0.869, respectively.Conclusion: In summary, compression degree of TN and type of conflicting vessels can determine short- and long-term CPR in adult patients with PTN after MVD.Keywords: compression degree of trigeminal nerve, type of conflicting vessels, microvascular decompression, sufficient decompression of trigeminal nerve, complete pain relief, primary trigeminal neuralgia

Ting-Ting Yang,1,&ast; Ze-Yi Wang,1,&ast; Ze-Xin Fan,1 Bo-Yi Yuan,1 Lin Ma,1 Jian-Feng Lu,1 Pen-Ju Liu,1 Yang He,2 Guang-Zhi Liu1 1Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China; 2Department of Neurology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang-Zhi Liu, Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of China, Tel +86-10-64456149, Fax +86-10-64456119, Email guangzhi2002@hotmail.comObjective: This study aimed to initially investigate the efficacy and safety of low-dose tocilizumab combined with glucocorticoid for the treatment of very-late-onset myasthenia gravis (VLOMG).Methods: We conducted a retrospective study in VLOMG patients who were administered intravenous methylprednisolone therapy and subsequently received low-dose oral corticosteroid, in combination with intravenous injection of tocilizumab given once every month for three months.Results: Five patients (mean age 75.0 ± 4.5 years) were included, and all of them were new-onset, and anti-acetylcholine receptor (AChR) antibody-positive generalized MG. The Quantitative Myasthenia Gravis Scale (QMGS) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before treatment were 15.4 ± 4.3 and 9.6 ± 2.3, respectively, and they exhibited a continuously decreasing trend after the first, second, and third injection of tocilizumab until 6 months after treatment. At 6 months post-treatment, the QMGS and MG-ADL scores were 5.0 ± 2.9 and 2.0 ± 1.2, respectively, and the difference between scores at baseline and 6-month follow-up was significant (P = 0.005 and P < 0.0001, respectively). No serious adverse drug reactions were reported in any patient during the study period.Discussions and Conclusion: The therapeutic efficacy of tocilizumab in VLOMG remains uncertain. The results from our study support the efficacy and safety of this combination treatment option for VLOMG, and strongly suggests the therapeutic potential of tocilizumab in VLOMG. However, considering the limitation of retrospective nature and small sample size in this study, prospective randomized controlled studies including a larger sample size of selected patients are needed to validate our results.Keywords: very late-onset myasthenia gravis, immunotherapy, tocilizumab, glucocorticoid

Judith Owokuhaisa,1 Jeremy I Schwartz,2,3 Matthew O Wiens,4,5 Pius Musinguzi,6 Godfrey Zari Rukundo7 1Faculty of Medicine, Department of Physiotherapy, Mbarara University of Science and Technology, Mbarara, Uganda; 2Uganda Initiative for Integrated Management of Non-Communicable Diseases, Kampala, Uganda; 3Section of General Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; 4Institute for Global Health, British Colombia Children’s Hospital, Vancouver, British Columbia, Canada; 5Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada; 6Department of Nursing, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 7Department of Psychiatry, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Judith Owokuhaisa, Email jowokuhaisa@must.ac.ugBackground: Proper discharge planning enhances continuity of patient care, reduces readmissions, and ensures safe and timely transition from health facility to home-based care. The current study aimed at exploring the healthcare providers’ perspectives of discharge planning among older adults, with respect to barriers and facilitators within the Ugandan health system.Methods: We conducted a qualitative exploratory study that used one-on-one interviews (Additional file 1) to describe individual perspectives of healthcare providers in their routine clinical care setting. The study included medical doctors (including consultants and physicians), nurses and physiotherapists directly involved in providing care to older adults. We conducted 25 in-depth interviews among healthcare providers for older adults with non-communicable diseases. The audio-recorded interviews were transcribed verbatim. Data were manually organized using a framework matrix guided by the COM-B domains (capability, opportunity and motivation) as the broad themes and sub-themes (physical and psychological capability, social and physical opportunity, reflective and automatic motivation) that influence behavior change (discharge planning).Results: Discharge planning was facilitated by availability of discharge forms, continuous medical education and working experience. The barriers to discharge planning were understaffing, workload/insufficient time, lack of discharge planning guidelines, lack of multidisciplinary approach and congested inpatient wards. Both barriers and facilitators were at various levels of healthcare service delivery such as patient, caregiver, healthcare provider, health facility and policy levels.Conclusion: Barriers to discharge planning spread across all levels of healthcare service delivery, but they can be addressed by enhancing the facilitators. This calls for a multi-level action to ensure adequate and quality patient care during and after hospitalization.Keywords: discharge planning, barriers, facilitators, COM-B framework

Catherine Atuhaire,1 Laura Brennaman,1 Grace Nambozi,1 Kabanda Taseera,2 Esther C Atukunda,3 Joseph Ngonzi,4 Daniel Atwine,5 Lynn T Matthews,6,7 Godfrey Zari Rukundo8 1Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 2Department of Microbiology, Mbarara University of Science and Technology, Mbarara, Uganda; 3Department of Pharmacy, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Obstetrics & Gynaecology, Mbarara University of Science and Technology, Mbarara, Uganda; 5SOAR Research Foundation, Mbarara, Uganda; 6Division of Infectious Diseases and Center for Global Health Massachusetts General Hospital, Boston, MA, USA; 7Division of Infectious Disease, University of Alabama at Birmingham, Birmingham, AL, USA; 8Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Catherine Atuhaire, Email catuhaire@must.ac.ugBackground: The Edinburgh Postnatal Depression Scale (EPDS) is a widely acknowledged screening tool for postpartum depression (PPD) globally, but its validation in Uganda has been lacking. This study aimed to assess the EPDS’s accuracy as a PPD screening tool in Uganda compared to the Mini-International Neuropsychiatric Interview (MINI 7.0.2) based on the DSM-5.Methods: This was a descriptive cross-sectional study conducted at a referral hospital and two peri-urban primary care postpartum clinics in rural southwestern Uganda. We enrolled 287 mothers aged 18 to 49 at their six-week postpartum visit. The EPDS was used for initial screening, and the MINI 7.0.2 was employed for clinical diagnosis. The study used the Runyankore-Rukiga language version of the EPDS and collected data from November 11, 2019, to June 10, 2020, with the MINI 7.0.2 as the reference standard.Results: The overall PPD prevalence was 29.5%, as opposed to 26.5% with EPDS and MINI 7.0.2 DSM-5 criteria (p = 0.239). The EPDS demonstrated a sensitivity of 86.8%, specificity of 92.1%, positive predictive value of 80.5%, and negative predictive value of 94.9%. A cutoff score of ≥ 10 was found to be the most effective acceptable point after drawing the AUC of ROC and determining the most appropriate point using Youden’s index. The area under the ROC curve, indicating the scale’s overall performance against MINI 7.0.2, was 0.89 for Bwizibwera HCIV, 0.97 for Kinoni HCIV, and 0.84 for MRRH. In conclusion, the EPDS can effectively screen for postpartum depression in southwestern Uganda using a cutoff score of ≥ 10. It exhibits strong diagnostic performance in correctly identifying PPD in postpartum mothers.Keywords: validation, EPDS, DSM-5, MINI, postpartum depression

Enhanced particle transport events are discovered and analyzed as the density limit of the J-TEXT tokamak is approached. Edge shear layer collapse is observed and the ratio of Reynolds power to turbulence production decreases. Simultaneously, the divergence of turbulence internal energy flux (i.e. turbulence spreading) increases, indicating that shear layer collapse triggers an outward spreading event. Studies of correlations show that the enhanced particle transport events are quasi-coherent, and manifested primarily in density fluctuations which exhibit positive skewness. Electron adiabaticity emerges as the critical parameter which signals transport event onset. For α < 0.35 as density approaches the Greenwald density, both turbulence spreading and density fluctuations rise rapidly. Taken together, these results elucidate the connections between edge shear layer, density fluctuations, particle transport events, turbulence spreading and plasma edge cooling as the density limit is approached.

Hui Wu,1– 3 Gui Zhen Weng,1 Li Na Sun,2 Zhang Chi Pan,1 Lu Zhang,4 Qiang Chen,1,3 Chun Mei Shi1,3 1Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 2Department of Oncology, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, 323000, People’s Republic of China; 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, 350001, People’s Republic of China; 4Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of ChinaCorrespondence: Chun Mei Shi, Email shichunmei@tom.comPurpose: Immune checkpoint inhibitors (ICIs) have been developed for clinical application and proven effective for non-small cell lung cancer (NSCLC). Blockade of the programmed cell death 1 (PD-1) protein can partially reinvigorate circulating exhausted-phenotype CD8+ T cells (Tex cells) in preclinical models, however the clinical implication in anti-PD-1-based immunotherapy in NSCLC is unknown.Methods: Serum specimens were obtained before and during treatment from 145 patients with NSCLC patients who received anti-PD-1 treatment and their prognoses were followed-up. Indicators such as cell subpopulations, T cell invigoration were detected by clinical laboratory testing. Survival curves were estimated by the Kaplan-Meier method, Cox regression analysis was used to identify factors associated with prognoses of NSCLC patients.Results: The expressions of Ki-67 in PD-1+/CD8+ T cells in most NSCLC patients (97 of 145 cases) increased after treatment. The responding Ki-67+/CD8+ T cell population was mainly CD45RAlo CD27hi, containing cells with high expression of CTLA-4, PD-1, and 2B4 and low expression of NKG2-D (P < 0.0001). The maximum fold change of Ki-67+/PD-1+/CD8+T cells in treatment cycles and the tumor burden determined by imaging may be associated with survival. Patients with higher Ki-67 expression on PD-1+CD8+ T-cells (pretreatment) had statistically significant increased progression-free survival (PFS). A Ki-67 expression to tumor burden ratio greater than 0.6 at the 1st cycle of anti-PD-1 immunotherapy was associated with improvement of PFS and overall survival (P < 0.05).Conclusion: Activation of circulating Tex cells before or during therapy related to tumor burden may be associated with clinical efficacy of anti-PD-1 immune therapy in NSCLC.Keywords: non-small cell lung cancer, immunotherapy, T cell invigoration, prognosis

Guo-Zhou Wang,1,&ast; Li-Hua Yang,1,&ast; Chao Gao2 1Department of Breast Tumor Surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei Province, 435000, People’s Republic of China; 2Department of General Practitioner, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei Province, 435000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Gao, Department of General Practitioner, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, 141 Tianjin Road, Huangshigang District, Huangshi, Hubei Province, 435000, People’s Republic of China, Email gaochaotongxue1987@163.comBackground: There is a lack of targeted therapies for triple-negative breast cancer (TNBC), necessitating the search for novel targets. Patients with TNBC exhibit elevated expression of neuron-specific septin-3 (SEPTIN3), leading to poor prognosis. This study aimed to investigate the modulation of SEPTIN3 expression in TNBC cells.Methods: The relative expression levels of SEPTIN3 in TNBC tissues and cell lines were determined using Western blotting and qRT-PCR. We generated lentivirally transduced TNBC cell lines so such that SEPTIN3 was overexpressed or knocked down. Next, the effect of SEPTIN3 on the biological behavior of TNBC cells was detected using a series of functional assays, including CCK8, colony formation, scratch, and transwell assays. We monitored the tumorigenicity of SEPTIN3 overexpressed cells and performed Ki-67 immunostaining in mice. The mechanism mediated by SEPTIN3 was studied using functional enrichment analysis and Western blotting.Results: Protein and mRNA expression levels of SEPTIN3 were observed to be increased in TNBC tissues and cell lines. SEPTIN3 knockdown reduced cell growth, invasion, and migration, whereas SEPTIN3 overexpression exerted the opposite effects. SEPTIN3 was observed to favor cell growth and tumorigenicity in vivo. In addition, SEPTIN3 promoted TNBC cell aggressiveness and proliferation via activation of the Wnt signaling pathway.Conclusion: SEPTIN3 emerged as an oncogene that accelerates tumor progression by regulating the Wnt signaling pathway.Keywords: triple-negative breast cancer, SEPTIN3, proliferation, invasion, Wnt signaling pathway

Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51-High tumours had shorter progression-free and overall survival compared to RAD51-Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR-proficient cancers (Myriad HRDscore

Recent emphasis and requirements for open data publication have led to significant increases in data availability in the Earth sciences, which is critical to long-tail data integration. Currently, data are often published in a repository with an identifier and citation, similar to those for papers. Subsequent publications that use the data are expected to provide a citation in the reference section of the paper. However, the format of the data citation is still evolving, particularly with regards to citing dynamic data, subsets, and collections of data. Considering the motivations of both data producers and consumers, the most pressing need is to create user-friendly solutions that provide credit for data producers and enable accurate citation of data, particularly integrated data. Providing easy-to-use data citations is a critical foundation that is required to address the socio-technical challenges around data integration. Studies that integrate data from dozens or hundreds of datasets must often include data citations in supplementary material due to page limits. However, citations in the supplementary material are not indexed, making it difficult to track citations and thus giving credit to the data producer. In this paper, we discuss our experiences and the challenges we have encountered with current citation guidance. We also review the relative merits of the currently available mechanisms designed to enable compact citation of collections of data, such as data collections, data papers, and dynamic data citations. We consider these options for three data producer scenarios: a domain-specific data collection, a data repository, and a large-scale, multidisciplinary project. We posit that a new mechanism is also needed to enable citation of multiple datasets and credit to data producers.

Ze-Jun Jin, Gen-Zhen Wang Department of Nephrology, Anhui Wannan Rehabilitation Hospital, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Gen-Zhen Wang, Email guanpa7947285@163.comObjective: This study aimed to analyze the clinical efficacy of dapagliflozin in the treatment of diabetic kidney disease and its impact on proteinuria levels in patients.Methods: Retrospective analysis of medical records of 176 patients with diabetic kidney disease treated at our hospital from January 2020 to January 2022. According to the different treatment methods, the patients were divided into a control group (n=88) receiving enalapril maleate treatment and an observation group (n=88) receiving dapagliflozin treatment. The clinical treatment effects, blood glucose levels, renal function indicators, inflammation factor indicators, and adverse reactions were compared between the two groups.Results: The total effective rate of treatment (97.73%) in the observation group was significantly higher than that (79.55%) in the control group (P< 0.05). After treatment, the FPG, 2hPG, and HbAlc levels in the observation group were significantly lower than those in the control group (P< 0.05). After treatment, the Scr, BUN, UmAlb, UAER, UACR, and 24-hour urine protein quantitative levels in the observation group were significantly lower than those in the control group (P< 0.05). After treatment, the hs-CRP, IL-1β, and TNF-α levels in the observation group were significantly lower than those in the control group (P< 0.05). The incidence of adverse reactions in the observation group significantly lower than the control group (P< 0.05).Conclusion: Compared with enalapril maleate alone, the combined application of dapagliflozin in the treatment of diabetic kidney disease has more significant clinical efficacy. It can further control patients’ blood sugar, reduce their body’s inflammatory response, alleviate or eliminate their proteinuria symptoms, promote the recovery of their renal function, and enhance the safety of their treatment to a certain extent, which helps to further improve the clinical treatment effect of patients.Keywords: stroke, nursing, hemiplegic limb rehabilitation training nursing, effect analysis

This study investigates human-building interaction in office spaces across multiple countries including Brazil, Italy, Poland, Switzerland, the United States, and Taiwan. We analyze social-psychological, contextual, and demographic factors to explain cross-country differences in adaptive thermal actions (i.e. cooling and heating behaviors) and conformity to the norms of sharing indoor environmental control features, an indicator of energy consumption. Specifically, personal adjustments such as putting on extra clothes are generally preferred over technological solutions such as adjusting thermostats in reaction to thermal discomfort. Social-psychological factors including attitudes, perceived behavioral control, injunctive norms, and perceived impact of indoor environmental quality on work productivity influence occupants’ intention to conform to the norms of sharing environmental control features. Lastly, accessibility to environmental control features, office type, gender, and age are also important factors. These findings demonstrate the roles of social-psychological and certain contextual factors in occupants’ interactions with building design as well as their behavior of sharing environmental control features, both of which significantly influence building energy consumption, and thus, broader decarbonization.

Zheng Liu,1 Qian Wang,1 Hui Wang,1 Jing Li,1 Ying Yuan,2 Guo-zhen Yi1 1Department of Respiratory Medicine, the Petroleum Clinical Medical College of Hebei Medical University, Langfang, People’s Republic of China; 2Department of Respiratory Medicine, the Langfang Third Hospital, Langfang, People’s Republic of ChinaCorrespondence: Zheng Liu, Department of Respiratory Medicine, the Petroleum Clinical Medical, College of Hebei Medical University, No. 51 of Xinkai Road, Guangyang District, Langfang, Hebei, 065000, People’s Republic of China, Tel +863162077814, Email zhengl06drsun@163.comBackground: To look at the differences and similarities in albumin and lipid metabolism in non-severe COVID-19 infection, non-severe community-acquired pneumonia, and severe community pneumonia with underlying diseases, as well as the relationship between albumin and lipid metabolism and inflammatory mediators.Methods: This retrospective analysis comprised 253 individuals with bacterial pneumonia and COVID-19 infection (1 May 2021– 1 May 2022). Routine blood examination, blood lipid levels, albumin level, C-reactive protein (CRP) levels, coagulation function, cardiac enzymes, liver function, renal function, immunological function, and bacterial culture were also collected. Correlation analysis was performed using Spearman’s test for lipid parameter and Inflammatory factors in the blood. Furthermore, the multiple linear regression (MLR) analysis was employed to analyze the multicollinearity in lipidomics data. The statistical analysis was performed using SPSS statistic version 19.0.Results: There were 63 (24.90%) non-severe community-acquired pneumonia patients (NSCAP), 48 (18.97%) severe community-acquired pneumonia patients (SCAP), 112 (44.27%) non-severe COVID-19 infection patients (NSCOV), and 30 (11.86%) healthy volunteers (HV). In all, 45.59% (116/253) of the patients had underlying diseases. Patients with community-acquired pneumonia had lower albumin and cholesterol levels than those with non-severe COVID-19 infection and healthy controls (t = − 3.81, − 2.09, P = 0.00, 0.04). Albumin, triglyceride, cholesterol, and LDL-C levels in peripheral blood were considerably lower in the SCAP group than in the NSCAP group. Albumin, cholesterol, HDL-C, LDL-C, and aop-A were all inversely connected with CRP in the SCAP with underlying illness group, but cholesterol level was favorably correlated with lymphocyte count (R = 0.36, P = 0.01). Hypoproteinemia, hypotriglyceridemia, and an elevated neutrophil-to-lymphocyte count ratio are all risk factors for severe community-acquired pneumonia.Conclusion: Hypoalbuminemia and abnormal lipid metabolism are important indicators of bacterial infection, especially severe bacterial pneumonia.Keywords: bacterial pneumonia, COVID-19, hypoproteinemia, lipids

Ya-Hui Hu,1 Gui-Zhou Li,1,2 Jia-Yi Long,1,2 Qing-Yan Yang,1,2 Yong Zhang,1 Feng Chen,1 Yong-Ren Wang3 1Department of Pharmacy, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Department of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yong-Ren Wang, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, 210008, People’s Republic of China, Email wangyongren@gmail.comAbstract: Vincristine-induced peripheral neuropathy (VIPN) is a common adverse effect of vincristine (VCR) for which there is no preventative or curative treatment. Here, we report a case of a patient suffering from severe VCR-related neurotoxicity. To explore the possible causes of severe VIPN in this patient, a set of genes involved in VCR metabolism, transport or are related to the cytoskeleton, microtubules, and inherited neurological diseases gene polymorphisms were examined via pharmacogenetic analyses. The genotyping results revealed the presence of a complex pattern of polymorphisms in CYP3A5, ABCC2, SYNE2, BAHD1, NPSR1, MTNR1B, CEP72, miR-4481 and miR-3117. A comprehensive understanding of all the pharmacogenetic risk factors for VIPN may explain the occurrence of severe neurotoxicity in our patient. This case brings to light the potential importance of pharmacogenetic testing in clinical practice. It also exemplifies the importance of developing early-detection strategies to optimize treatment regimens through prior risk stratification while reducing adverse drug reactions and personalizing therapy.Keywords: vincristine, peripheral neuropathy, pharmacogenetics, toxicity, polymorphisms, precision medicine

We present BVRI and unfiltered light curves of 93 Type Ia supernovae (SNe Ia) from the Lick Observatory Supernova Search (LOSS) follow-up program conducted between 2005 and 2018. Our sample consists of 78 spectroscopically normal SNe Ia, with the remainder divided between distinct subclasses (3 SN 1991bg-like, 3 SN 1991T-like, 4 SNe Iax, 2 peculiar, and 3 super-Chandrasekhar events), and has a median redshift of 0.0192. The SNe in our sample have a median coverage of 16 photometric epochs at a cadence of 5.4 d, and the median first observed epoch is ∼4.6 d before maximum B-band light. We describe how the SNe in our sample are discovered, observed, and processed, and we compare the results from our newly developed automated photometry pipeline to those from the previous processing pipeline used by LOSS. After investigating potential biases, we derive a final systematic uncertainty of 0.03 mag in BVRI for our data set. We perform an analysis of our light curves with particular focus on using template fitting to measure the parameters that are useful in standardizing SNe Ia as distance indicators. All of the data are available to the community, and we encourage future studies to incorporate our light curves in their analyses.

The mission of HL-2A is to explore the key physical topics relevant to ITER and to the advanced tokamak operation (e.g. the operation of future HL-2M), such as the access of H-mode, energetic particle physics, edge-localized mode (ELM) mitigation/suppression and disruption mitigation. Since the 2016 Fusion Energy Conference, the HL-2A team has focused on the investigations on the following areas: (i) pedestal dynamics and L-H transition, (ii) techniques of ELM control, (iii) turbulence and transport, (iv) energetic particle physics. The HL-2A results demonstrated that the increase of mean shear flow plays a key role in triggering L-I and I-H transitions, while the change of flow is mainly induced by the ion pressure gradient. Both mitigation and suppression of ELMs were realized by laser blow-off seeded impurity (Al, Fe, W). The 30% Ne mixture supersonic molecular beam injection seeding also robustly induced ELM mitigation. The ELMs were mitigated by low-hybrid current drive. The stabilization of m/n = 1/1 ion fishbone activities by electron cyclotron resonance heating was found on the HL-2A. A new m/n = 2/1 ion fishbone activity was observed recently, and the modelling indicated that passing fast ions dominantly contribute to the driving of 2/1 fishbone. The non-linear coupling between the toroidal Alfven eigenmode and tearing mode (TM) led to the generation of a high frequency mode with the toroidal mode number n = 0. The turbulence was modulated by TM when the island width exceeds a threshold and the modulation is localized merely in the inner area of the islands. Meanwhile, turbulence radial spread took place across the island region.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachón in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg 2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320-1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg 2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ∼27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.

Zhendong Li,1,&ast; Chenliang Zhou,2,&ast; Qing Peng,3,&ast; Suguo Wang,3 Guowei Qian,2 Lina Tang,2 Xin Zhou,4 Qingcheng Yang,1 Zan Shen,2 GaoZhong Huang,3 Yonggang Wang,2 Hongtao Li2 1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 3Department of VIP Clinic, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 4Cancer Research Institute of Jilin University, the First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonggang Wang; Hongtao Li, Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yishan Road, Xu Hui District, Shanghai, 200233, People’s Republic of China, Tel +086-021-24058408, Email sirui666@163.com; Lhtmed@126.comPurpose: Inflammatory response and nutritional status are associated with cancer development and progression. The present study aimed to evaluate the predictive ability of the fibrinogen–albumin ratio index (FARI) to the efficacy of neoadjuvant chemotherapy (NAC) for osteosarcoma.Patients and methods: A retrospective analysis involving 752 consecutive osteosarcoma patients between 2012 and 2020 was performed. Data on serum fibrinogen, albumin levels, white blood cell count, platelet count, and alkaline phosphatase (ALP) before and after NAC were collected. The predictive value of the NAC efficacy in osteosarcoma was assessed by constructing a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Prognosis and its predictive factors were analyzed by Kaplan–Meier method and COX regression analysis. Nomogram was established according to selected variables. The predictive performance of the nomogram model was assessed using C-statistics.Results: A total of 203 patients were included. ROC analysis showed that both FARI before NAC (preFARI; AUC = 0.594, p = 0.032) and the change in FARI before and after NAC (dfFARI = preFARI-postFARI; AUC = 0.652, p = 0.001) exhibited more favorable predictive ability than ALP and other inflammation markers. The preFARI was divided into the high group (> 6.1%) and the low group (≤ 6.1%) based on the optimal cut-off value of 6.1%. Patients with a high preFARI showed significantly decreased metastasis-free survival (MFS) and disease-free survival (DFS) (all p< 0.01). In multivariable analysis, preFARI was an independent prognostic marker for patients with osteosarcoma. Predictive nomograms exhibited good ability to predict MFS (C-index = 0.748, se = 0.028) and DFS (C-index=0.727, se = 0.030).Conclusion: Our findings indicated that FARI exhibits the favorable predictive ability for the efficacy of NAC for osteosarcoma, which could support clinicians and patients in clinical decision-making and treatment optimization.Keywords: osteosarcoma, neoadjuvant chemotherapy, fibrinogen, albumin, fibrinogen–albumin ratio index, prognosis

Edith K Wakida,1,2 Godfrey Z Rukundo,3 Clara Atuhaire,1 Christine K Karungi,1 Edward Kumakech,4 Jessica E Haberer,5,6 Zohray M Talib,2 Celestino Obua7 1Office of Research Administration, Mbarara University of Science and Technology, Mbarara, Uganda; 2Department of Medical Education, California University of Science and Medicine, San Bernardino, CA, USA; 3Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Nursing and Midwifery, Lira University, Lira, Uganda; 5Center for Global Health, Massachusetts General Hospital, Boston, MA, USA; 6Department of Medicine, Harvard Medical School, Boston, MA, USA; 7Office of the Vice Chancellor, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Edith K Wakida, Office of Research Administration, Mbarara University of Science and Technology, Mbarara, Uganda, Tel +256 782 685541, Email ediwakida@must.ac.ugPurpose: To evaluate the perceptions of undergraduates and mentors on the appropriateness, acceptability, and feasibility of a mentored seed-grant (micro-research) by Health Professions Education Partnership Initiative - Transforming Ugandan Institutions Training Against HIV/AIDS (HEPI-TUITAH) program on HIV training in Uganda.Methods: We conducted a cross-sectional descriptive qualitative study with focus groups, on HIV micro-research training, with undergraduate health professions students and faculty mentors across three partner institutions in rural Uganda.Results: A total of 24 students and 13 mentors (5– 8 per group) took part in the focus group discussions. Most participants stated that the HEPI-TUITAH micro-research program was acceptable, appropriate and feasible for health professions undergraduate students. The interprofessional education approach of bringing together students from different programs and years of study was valuable especially for peer mentorship. There was a need to provide for institution-based training in addition to the centrally organized training for the benefit of all the team members. Participants also noted a need for the program to find a way of providing the students with data collection experience even with the COVID-19 pandemic situation.Conclusion: The HEPI-TUITAH micro-research program was perceived as acceptable, appropriate, and feasible for health professions undergraduate students. It also promoted teamwork and academic collaboration. Provision for institution-based micro-research training activities and data collection experiences for the undergraduate students even during the COVID-19 pandemic would make the program more valuable. The lessons learnt will be applied to future training cohorts to optimize program impact and may be useful for similar programs in other settings.Keywords: HIV research training, mentored research, interprofessional education

Mark Mohan Kaggwa,1,2 Godfrey Zari Rukundo,1,2 Edith K Wakida,2– 4 Samuel Maling,1 Baker Makaya Sserumaga,1,2 Letizia Maria Atim,1,2 Celestino Obua5 1Department of Psychiatry, Mbarara University of Science and Technology, Mbarara, Uganda; 2African Centre for Suicide Prevention and Research, Mbarara, Uganda; 3Office of Research Administration, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Medical Education, California University of Science and Medicine, San Barnardino, CA, United States of America; 5Department of Pharmacology and Therapeutics, Mbarara University of Science and Technology, Mbarara, UgandaCorrespondence: Mark Mohan Kaggwa, Email kmarkmohan@gmail.comBackground: Suicide is one of the leading causes of death globally, accounting for about 800,000 deaths annually. The suicide burden drastically increased since the beginning of the COVID-19 pandemic. In Uganda, no known study has determined the suicide rate since the beginning of the COVID-19 pandemic.Objective: To determine the suicide mortality rate and describe the characteristics of victims of suicide attempts from January to December 2020 in south western Uganda.Methods: This study was based on the health management information systems (HMIS) of patients’ registered data for the year 2020 at 15 selected primary health care facilities in four districts in south-western Uganda. We used a data extraction tool to capture demographic and clinical characteristics of the individuals who had attempted or completed suicide. We estimated yearly incidence rates of fatal and non-fatal suicide attempts, and used chi-square and t-test to determine the statistical difference between suicide attempt outcomes.Results: A total of 130 non-fatal suicide attempts and 26 suicides were identified. Majority were male 69.87% (n = 109/156) and the mean age was 27.16 (SD = 14.71) years. The overall incidence of suicide attempts was about 60 attempts per 100,000 people, while that of completed suicide was about three deaths per 100,000 people. The suicide attempts increased following the first month of COVID-19 lockdown in the country (March 2020) and most individuals attempted suicide by poisoning (n = 144).Conclusion: Suicide is a common occurrence in primary health care settings of Uganda and there has been a rapid increase in suicide attempts since the onset of the COVID-19 pandemic. With suicide by poisoning being common, there is need for proactive interventions, such as the control of pesticides and herbicides, to prevent suicide among members of this community, especially during pandemic conditions.Keywords: suicide, non-fatal suicide attempt, suicide attempt, primary health care, COVID-19, pandemic, Uganda

Shu-Jie Pang,1,&ast; Zhe Sun,1,&ast; Wen-Feng Lu,1,&ast; Hui Si-Ma,1 Zhi-Peng Lin,2 Yang Shi,1 Ying-Cheng Yang,1 Xi-Jun Zhao,1 Guang-Shun Yang,1 Guang-Zhi Jin,3 Ning Yang1 1Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China; 2Department of Hepatobiliary Surgery, The 940th Hospital of CPLA Joint Logistics Support Force, Lanzhou, 730050, People’s Republic of China; 3Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang, Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China, Tel +86 21 81877591, Fax +86 21 6556 6851, Email lancet00@163.com Guang-Zhi Jin, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China, Email jgzhi@hotmail.comBackground: RBM10ʹs function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study.Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein–protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test.Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1.Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.Keywords: RBM10, hepatocellular carcinoma, prognosis, differentially expressed gene, integrated bioinformatics analysis

BackgroundThe Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry.Methods and resultsA total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Xin Zhou,1,2,&ast; Tian-Man Li,1– 3,&ast; Jian-Zhu Luo,1,2,&ast; Chen-Lu Lan,1,2 Zhong-Liu Wei,1,2 Tian-Hao Fu,1,2 Xi-Wen Liao,1,2 Guang-Zhi Zhu,1,2 Xin-Ping Ye,1,2 Tao Peng1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Key Laboratory of Early Prevention & Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital of Guangxi Medical University, Yulin, 537000, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Peng Email pengtaogmu@163.comBackground: Cytochrome P450 2C8 (CYP2C8) gene is one of the members of the cytochrome P450 enzymes (CYPs) gene family. The aim of this study was to reveal the function of CYP2C8 in hepatocellular carcinoma (HCC) and its effect on the sorafenib resistance.Methods: Differential expression analysis in multiple HCC datasets all suggested that CYP2C8 expression was significantly decreased in HCC tissues, compared with para-carcinoma liver tissues. The expression level of CYP2C8 was subsequently compared between HCC tissues and para-carcinoma liver tissues of 70 patients form Guangxi, China, with the result consistent with the above. Survival analysis and ROC analysis indicated that CYP2C8 was equipped with satisfactory diagnostic and prognostic value in HCC. To examine the effect of CYP2C8 on the malignant phenotype of HCC cells, stable transcriptional cell lines with CYP2C8 over-expression were established, and then Cell Counting Kit-8 (CCK8) assay, colony formation assay, cell cycle assay, cell invasion assay and wound healing assay were performed.Results: The results of aforementioned assays suggested that CYP2C8 over-expression restricted the proliferation, clonality, migration, invasion and cell cycle of HCC cells but had no significant effect on cell apoptosis. The enrichment analysis in terms of sequencing data of HCC cell lines with stable CYP2C8 over-expression suggested that CYP2C8 might be related to PI3K/Akt/p27Kip1 axis. The inhibition of CYP2C8 over-expression on PI3K/Akt/p27Kip1 axis was subsequently demonstrated with Western blot assay. In the rescue experiment, it was observed that both P27 inhibitor and PI3K agonist counteracted the repressed malignant phenotype caused by CYP2C8 over-expression, which further demonstrated that CYP2C8 played a role in HCC cells via PI3K/Akt/p27Kip1 axis.Discussion: The results demonstrated that CYP2C8 enhances the anticancer activity of sorafenib in vitro assays and in tumor xenograft model, with Ki-67 down-regulation and PI3K/Akt/p27Kip1 axis inhibition. In conclusion, these findings hinted that CYP2C8 restricted malignant phenotype and sorafenib resistance in HCC via PI3K/Akt/p27kip1 axis.Keywords: hepatocellular carcinoma, CYP2C8, sorafenib resistance, cell cycle

Noble Ajuna,1 Brian Tumusiime,1 Joseph Amanya,1 Sharon Awori,1 Godfrey Z Rukundo,2 John Baptist Asiimwe1 1Department of Nursing, Bishop Stuart University, Mbarara City, Southwestern Uganda; 2Department of Psychiatry, Mbarara University of Science and Technology, Mbarara City, Southwestern UgandaCorrespondence: John Baptist Asiimwe Tel +256 775979015; +256 751300773Email johnbaptistasiimwe.2008@gmail.comBackground: Young adults living with HIV (YALWH) struggle to maintain high levels of adherence to antiretroviral therapy (ART) because of numerous barriers. This study describes the social networks of YALWH (18– 24 years), their barriers to ART adherence, and the perceived role of social networks in overcoming those barriers.Methods: This study used a qualitative descriptive research design. Twenty-three (23) YALWH who were on ART for a period of greater than one (1) month and had consented to participate in the study were purposively selected from two primary health care facilities in southwestern Uganda. We held four (4) focus group discussions with the YALWH over 5 weeks between the 24th of July and 7th September 2020. Data were audio recorded, transcribed, and entered in Microsoft word 2010. Using the content analysis techniques, data were inductively coded and categories or themes developed.Results: Most YALWH belonged to bonding (family, friends, and neighbors), followed by bridging (informal groups), and linking (health professionals) social networks, respectively. Most YALWH, irrespective of gender, had close connections with their mothers or elder sisters. The commonest form of bridging networks was informal community groups that provided financial services, whereas the linking ones comprised health professionals’ directly involved in HIV patient care such as nurses, counselors, and their affiliates (expert clients or clinic based peer supporters), who occasionally acted as bonding networks. Structural barriers to ART adherence (eg, stigma) were the most cited, followed by medication- (eg, pill burden), and patient-related barriers (eg, non-disclosure of HIV status). Bonding networks were perceived to help overcome patient, medication, and structural barriers to ART adherence. Bridging networks overcame structural and medication-related barriers to ART adherence. Linking networks were perceived to help overcome some health systems and medication-related barriers to ART adherence.Conclusion: Bonding social networks seem to play a prominent role in overcoming numerous barriers to ART adherence compared with bridging and linking social networks.Keywords: HIV, ART adherence, barriers, social networks, YALWH, perceived role

Ron Firestein,1,2,&ast; Cezary Marcinkiewicz,3,4,&ast; Linyan Nie,5 Hui Kheng Chua,1,2 Ines Velazquez Quesada,4 Marco Torelli,6 Mark Sternberg,3 Bojana Gligorijevic,4 Olga Shenderova,6 Romana Schirhagl,5 Giora Z Feuerstein3 1Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia; 2Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, 3800, Australia; 3Debina Diagnostics Inc., Newtown Square, PA, USA; 4College of Engineering, Department of Bioengineering, Temple University, Philadelphia, PA, USA; 5Groningen University, Groningen, 9727, the Netherlands; 6Adámas Nanotechnologies, Inc., Raleigh, NC, 27617, USA&ast;These authors contributed equally to this workCorrespondence: Giora Z FeuersteinDebina Diagnostics Inc., 33 Bishop Hollow Road, Newtown Square, PA, 19073, USATel +4842221575Email giorafeuerstein@gmail.comBackground: We recently reported on preferential deposition of bare fluorescent diamond particles FDP-NV-700/800nm (FDP-NV) in the liver following intravenous administration to rats. The pharmacokinetics of FDP-NV in that species indicated short residency in the circulation by rapid clearance by the liver. Retention of FDP-NV in the liver was not associated with any pathology. These observations suggested that cancer therapeutics, such as doxorubicin, linked to FDP-NV, could potentially serve for anti-cancer treatment while sparing toxicities of peripheral organs.Purpose: To generate proof-of-concept (POC) and detail mechanisms of action of doxorubicin-coated FDP-NV-700/800nm (FDP-DOX) as a prospective chemotherapeutic for metastatic liver cancer.Methods: FDP-DOX was generated by adsorption chemistry. Experimental design included concentration and time-dependent efficacy studies as compared with naïve (baren) FDP-NV in in vitro liver cancer cells models. Uptake of FDP-NV and FDP-DOX by HepG-2, Hep-3B and hCRC organoids were demonstrated by flow-cytometry and fluorescent microscopy. FDP-DOX pharmacodynamic effects included metabolic as well as cell death biomarkers Annexin V, TUNEL and LDH leakage. DOX desorpted from FDP-DOX was assessed by confocal microscopy and chemical assay of cells fractions.Results: FDP-DOX efficacy was dose- and time-dependent and manifested in both liver cancer cell lines and human CRC organoids. FDP-DOX was rapidly internalized into cancer cells/organoids leading to cancer growth inhibition and apoptosis. FDP-DOX disrupted cell membrane integrity as evident by LDH release and suppressing mitochondrial metabolic pathways (AlamarBlue assay). Access of free DOX to the nuclei was confirmed by direct UV-Visible fluorescent assay and confocal microscopy of DOX fluorescence.Conclusion: The rapid uptake and profound cancer inhibition observed using FDP-DOX in clinically relevant cancer models, highlight FDP-DOX promise for cancer chemotherapeutics. We also conclude that the in vitro data justify further investment in in vivo POC studies.Keywords: liver cancer cell-lines, human colorectal cancer organoids, fluorescent diamond particles-NV-700/800nm, doxorubicin, apoptosis

Metadata describe the ancillary information needed for data preservation and independent interpretation, comparison across heterogeneous datasets, and quality assessment and quality control (QA/QC). Environmental observations are vastly diverse in type and structure, can be taken across a wide range of spatiotemporal scales in a variety of measurement settings and approaches, and saved in multiple formats. Thus, well-organized, consistent metadata are required to produce usable data products from diverse environmental observations collected across field sites. However, existing metadata reporting protocols do not support the complex data synthesis and model-data integration needs of interdisciplinary earth system research. We developed a metadata reporting framework (FRAMES) to enable management and synthesis of observational data that are essential in advancing a predictive understanding of earth systems. FRAMES utilizes best practices for data and metadata organization enabling consistent data reporting and compatibility with a variety of standardized data protocols. We used an iterative scientist-centered design process to develop FRAMES, resulting in a data reporting format that incorporates existing field practices to maximize data-entry efficiency. Thus, FRAMES has a modular organization that streamlines metadata reporting and can be expanded to incorporate additional data types. With FRAMES's multi-scale measurement position hierarchy, data can be reported at observed spatial resolutions and then easily aggregated and linked across measurement types to support model-data integration. FRAMES is in early use by both data originators (persons generating data) and consumers (persons using data and metadata). In this paper, we describe FRAMES, identify lessons learned, and discuss areas of future development.

Data quality control is one of the most time consuming activities within Research Infrastructures (RIs), especially when involving observational data and multiple data providers. In this work we report on our ongoing development of data rogues, a scalable approach to manage data quality issues for observational data within RIs. The motivation for this work started with the creation of the FLUXNET2015 dataset, which includes carbon, water, and energy fluxes plus micrometeorological and ancillary data measured in over 200 sites around the world. To create an uniform dataset, including derived data products, extensive work on data quality control was needed. The unpredictable nature of observational data quality issues makes the automation of data quality control inherently difficult. Developed based on this experience, the data rogues methodology allows for increased automation of quality control activities by systematically identifying, cataloging, and documenting implementations of solutions to data issues. We believe this methodology can be extended and applied to others domains and types of data, making the automation of data quality control a more tractable problem.

Mei-Xiang Zhan,1,2,* Li Tang,3,* Yun-Fei Lu,4,* Huang-Hui Wu,1,* Zhi-Bin Guo,1 Zhong-Mou Shi,1 Chen-Long Yang,1 Yi-Qing Zou,1,2 Fei Yang,1,2,5 Guo-Zhong Chen1,2 1Department of Anesthesiology and Perioperative Medicine, Clinical Medical College, (900 Hospital of the Joint Logistic Support Force), Fujian Medical University, Fuzhou, Fujian, 350025, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, Fujian, 350025, People’s Republic of China; 3Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 4Department of Anesthesiology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 5Laboratory of Pain Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350122, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Zhong Chen; Fei YangDepartment of Anesthesiology and Perioperative Medicine, 900 Hospital of the Joint Logistic Support Force, Fujian Medical University, #156 West 2 nd Ring Road North, Gulou District, Fuzhou, 350025, People’s Republic of ChinaEmail cgzssq2000@sina.com; yangfeimedbrain@outlook.comIntroduction: Ulinastatin, a broad-spectrum serine protease inhibitor, has been widely used to treat various diseases clinically. However, so far, the antinociceptive effect of ulinastatin remains less studied experimentally and the underlying mechanisms of ulinastatin for pain relief remain unclear. This study aimed to find evidence of the analgesic effect of ulinastatin on acute somatic and visceral pain.Methods: The analgesic effect of ulinastatin on acute somatic and visceral pain was evaluated by using formalin and acetic acid-induced writhing test. The analgesic mechanism of ulinastatin was verified by detecting the peripheral inflammatory cell infiltration and spinal glial activation with hematoxylin-eosin (H&E) and immunohistochemistry staining.Results: We found that both of intraperitoneal (i.p.) pre-administration and post-administration of ulinastatin could reduce the total number of flinching and the licking duration following intraplantar formalin injection in a dose-related manner. However, the inhibitory effect of ulinastatin existed only in the second phase (Phase 2) of formalin-induced spontaneous pain response, with no effect in the first phase (Phase 1). The formalin-induced edema and ulcer were also improved by i.p. administration of ulinastatin. Moreover, i.p. administration of ulinastatin was also able to delay the occurrence of acetic acid-induced writhing and reduced the total number of writhes dose-dependently. We further demonstrated that ulinastatin significantly decreased the local inflammatory cell infiltration in injured paw and peritoneum tissue under formalin and acetic acid test separately. The microglial and astrocytic activation in the spinal dorsal horn induced by intraplantar formalin and i.p. acetic acid injection were also dramatically inhibited by i.p. administration of ulinastatin.Conclusion: Our results for the first time provided a new line of evidence showing that ulinastatin could attenuate acute somatic and visceral pain by inhibiting the peripheral and spinal inflammatory reaction.Keywords: Ulinastatin, formalin, somatic pain, visceral pain, inflammation, antinociception

Asnake Balche Bade,1 Teshale Ayele Mega,2 Getandale Zeleke Negera3 1School of Pharmacy, Institute of Health Science, Arbaminch University, Arbaminch, Ethiopia; 2School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Clinical Pharmacy, School of Pharmacy, Institute of Health, Jimma University, Jimma, Oromia Regional State, EthiopiaCorrespondence: Teshale Ayele MegaAddis Ababa University, P.O. Box: 9086, Addis Ababa, EthiopiaTel +251 91 3144738Email tesh.ayu2016@gmail.comBackground: Clinicians use sputum culture conversion as an interim indicator of the efficacy of multi-drug resistant tuberculosis (MDR-TB) treatment and to determine treatment duration. Yet, limited studies have been published in Ethiopia.Objective: The objective of this study was to determine the predictors of delayed culture conversion among patients receiving MDR-TB treatment at selected treatment centers in Ethiopia.Patients and Methods: A multi-center observation study was conducted among MDR-TB patients in South and Southwestern Ethiopia from April 14 to May 14, 2019. The data of patients treated from January 2013 to July 2019 were reviewed using a data abstraction tool. The data were analyzed. Descriptive statistics was computed using SPSS version 21 software program. Cox regression was used to identify predictors of delayed culture conversion. Hazard ratios with a two-sided p-value < 0.05 were considered statistically significant.Results: Of 200 included MDR-TB patients, 108 (54%) were males. Majority,159 (79.5%) of the patients had a culture conversion time of less than two months, while 15 (7.5%) had delayed culture conversion (greater than 120 days). Patient’s registration group (after loss to follow- (adjusted hazard ratio (AHR)=16.215, 95% CI [3.839, 68.498]), after treatment failure (AHR=12.161, 95% CI [2.516, 58.793]), history of previous TB treatment (AHR=4.007, 95% CI [3.115, 62.990])) and low BMI (AHR= 1.257; 95% CI [0.725,1.547] were identified as a risk factors for delayed culture conversion.Conclusion: Our finding showed that nearly 80% of the patients achieve sputum culture conversion by the second month of treatment. Delayed culture conversion was more likely among patients with malnutrition (BMI< 18.5kg/m2), after treatment failure, previous TB treatment, and after lost to follow-up.Keywords: culture conversion, predictors, MDR-TB, Ethiopia

Yu Kang,1 Zi-Liang Hou,2 Guang-Zhong Yang,3 Xiao-Juan Wang,1 Wen-Ming Chen,3 Huan-Zhong Shi4 1Department of Internal Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Huan-Zhong Shi; Wen-Ming Chen Email shihuanzhong@sina.com; 13910107759@163.comPurpose: Pleural effusion (PE) is prevalent in “real-life” populations of multiple myeloma (MM), a common hematologic malignancy. Development of PE likely has prognostic implications. The aim of this study was to investigate the characteristics and identify risk factors for occurrence of PE in MM.Patients and Methods: We reviewed electronic medical records of 907 patients diagnosed with MM.Results: Incidence of PE in MM patients was 42.7%. Small and bilateral PE in most cases. PE developed in all MM subtypes, the median time from diagnosis of multiple myeloma to pleural effusion was 6.8 months (range 0.8– 33.6 months). Patients with PE showed worse survival than those without PE (unadjusted hazard ratio with 95% confidence interval: 2.249 [1.774– 2.852]). No difference in survival was found between patients with small PE and those with moderate to large PE (unadjusted HR, 1.402; 95% CI, 1.037– 1.896). Plasma cell proportion (OR, 1.373; 95% CI, 1.153– 1.634; P = 0.009) and amyloidosis (OR, 1.791; 95% CI, 1.408– 2.279; P = 0.024) were risk factors for the occurrence of PE at the initial diagnosis of MM. Plasma cell proportion (OR, 1.853; 95% CI, 1.451– 2.368; P = 0.038), pneumonia (OR, 1.309; 95% CI, 1.143– 1.498; P = 0.008) and heart failure (OR, 1.815; 95% CI, 1.387– 2.374; P = 0.031) were risk factors for the occurrence of PE at relapse of MM.Conclusion: The incidence of PE in MM patients is notable and PE can occur in all MM subtypes. PE indicates a poor prognosis, even small amounts of effusion. PE is a problem worthy of attention, especially in patients with high plasma cell proportion, amyloidosis or complicated with pneumonia and heart failure.Keywords: pleural effusion, multiple myeloma, incidence, risk factors, overall survival

Mark Mohan Kaggwa,1 Felix Bongomin,2 Sarah Maria Najjuka,3 Godfrey Zari Rukundo,1 Scholastic Ashaba1 1Department of Psychiatry, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; 2Department of Medical Microbiology and Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda; 3College of Health Sciences, Makerere University, Kampala, UgandaCorrespondence: Felix BongominDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Gulu University, P. O. Box 166, Gulu, UgandaTel +256-78452-3395Email drbongomin@gmail.comContext: Self-medication is becoming common during the coronavirus disease − 2019 (COVID-19) pandemic due to the increasing popularity of home-based management of asymptomatic and mild cases. In this case report, we describe a patient who developed manic symptoms as a result of self-medication with a regimen containing cannabis to manage COVID-19 symptoms.Case Details: A 52-year-old man with no prior history of a mental disorder, presented with a one-week history of talking more than usual, poor sleep, destructiveness, irritability, and altered mental status, following use of homemade remedies containing oranges, garlic, ginger, onions, honey, lemon, and cannabis to treat COVID-19 related symptoms over a 2-week period. This was his index presentation with such symptoms in his life. He had never used any substance of addiction before, did not have any known chronic medical condition, and had no family member with a history of any known mental illness. He was a suspect because his father had tested positive for COVID-19 and was undergoing treatment. He tested negative for COVID-19 after 3-weeks of initial COVID-19 like symptoms, urine sample was positive for tetrahydrocannabinol (THC), and he had normal investigations. He was managed with a mood stabilizer (oral carbamazepine at a dose of 200mg three times daily), antipsychotic (chlorpromazine 200mg twice daily), a sedative (diazepam 10mg at before bedtime), and occupational therapy. All manic symptoms resolved in a period of two weeks.Conclusion: Cannabis induced mental illness following self-medication for COVID-19 like symptoms is on the rise in the population. Due to increasing COVID-19 cases globally, hospital congestion, the popularity of home-based care guidelines for asymptomatic and mild COVID-19 to reduce hospital burden in many countries, and easy access to cannabis. With no approved cure for COVID-19, patients are turning to natural remedies to relieve symptoms of COVID-19. Emphasis on prevention of this insalubrious self-medication among the COVID-19 patients is needed to stop complication related to cannabis use.Keywords: COVID-19, cannabis, mania, bipolar, mental disorder, self-medication, cannabis-induced mania, homemade remedies for COVID-19, cannabis use complication