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Future climate presents conflicting implications for forest biomass. We evaluate how plant hydraulic traits, elevated CO2 levels, warming, and changes in precipitation affect forest primary productivity, evapotranspiration, and the risk of hydraulic failure. We used a dynamic vegetation model with plant hydrodynamics (FATES-HYDRO) to simulate the stand-level responses to future climate changes in a wet tropical forest in Barro Colorado Island, Panama. We calibrated the model by selecting plant trait assemblages that performed well against observations. These assemblages were run with temperature and precipitation changes for two greenhouse gas emission scenarios (2086-2100: SSP2-45, SSP5-85) and two CO2 levels (contemporary, anticipated). The risk of hydraulic failure is projected to increase from a contemporary rate of 5.7% to 10.1-11.3% under future climate scenarios, and, crucially, elevated CO2 provided only slight amelioration. By contrast, elevated CO2 mitigated GPP reductions. We attribute a greater variation in hydraulic failure risk to trait assemblages than to either CO2 or climate. Our results project forests with both faster growth (through productivity increases) and higher mortality rates (through increasing rates of hydraulic failure) in the neo-tropics accompanied by certain trait plant assemblages becoming nonviable.

Autophagy in eukaryotes functions to maintain homeostasis by degradation and recycling of long-lived and unwanted cellular materials. Autophagy plays important roles in pathogenicity of various fungal pathogens, suggesting that autophagy is a novel target for development of antifungal compounds. Here, we describe bioluminescence resonance energy transfer (BRET)-based high-throughput screening (HTS) strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 that is critical for autophagosome formation. We identified ebselen (EB) and its analogs ebselen oxide (EO) and 2-(4-methylphenyl)-1,2-benzisothiazol-3(2H)-one (PT) as inhibitors of fungal pathogens Botrytis cinerea and Magnaporthe oryzae ATG4-mediated ATG8 processing. The EB and its analogs inhibit spore germination, hyphal development, and appressorium formation in Ascomycota pathogens, B. cinerea, M. oryzae, Sclerotinia sclerotiorum and Monilinia fructicola. Treatment with EB and its analogs significantly reduced fungal pathogenicity. Our findings provide molecular insights to develop the next generation of antifungal compounds by targeting autophagy in important fungal pathogens.

Technology has expanded the landscape of higher education. The ability to learn almost anything from anywhere at any time has impacted educational attainment, particularly for those who lacked access in the past. Many who enter the virtual classroom, however, do not stay. Completion rates for online learning fall short, especially when compared to in-person experiences. For all its advancements, online learning has also created a chasm in human connection that influences learning. We are not made to connect through wires. Though we may espouse having multitudes of "friends" online, developing a true sense of belonging and connection must be purposefully developed when working through a screen and keyboard. This reflective essay interrogates the use of technology in higher education and encourages the inclusion of positive psychology practices to bridge the gap of human connection that is an integral part of student success.

Abstract Background The United Nations’ 95-95-95 (95% of people with HIV being aware of their diagnosis, 95% of those aware of their diagnosis being on treatment and 95% achieving viral suppression) target aims to reduce morbidity and mortality of HIV. However, with 60% of new HIV infections occurring in sub-Saharan Africa (SSA), achieving this target in the region is challenging. Viral load (VL) monitoring is the gold-standard approach of assessing treatment efficacy, and its implementation into national health systems is a global health priority if elimination of HIV as a public health threat is to be achieved by 2030. This systematic review aims to investigate VL monitoring outcomes in SSA, and to identify gaps and possible interventions to help nations meet their 2030 targets. Methods A literature search of three electronic platforms (MEDLINE, EMBASE and Global Health) was undertaken from 1 January to 9 August 2024 to identify studies published in English and conducted in SSA. The primary outcome was the proportion of people living with HIV (PLHIV) on antiretroviral therapy (ART) with routine VL monitoring at the recommended time points (initially, 6 months, 12 months and annually). Secondary outcomes reported proportions of PLHIV who received routine VL monitoring who went on to complete the cascade of care after identified virological failure [enhanced adherence counselling (EAC), switch to second-line ART, and finally viral suppression]. Results The initial search identified 342 papers, of which 35 studies were included for narrative synthesis. Included studies reported on findings from 14 African countries and demonstrated extensive variation in rates of VL monitoring (range: 24.3-99.7%, mean: 63.8%). Results were more unfavourable in the latter steps of the viral load monitoring cascade, with a range of 0-88%, and a switch to second-line ART mean of 42% (range: 4.4-93%). Studies with additional support, and those with community-based models of care, had higher rates of VL testing and viral suppression. Conclusions VL monitoring and management of virological failure are suboptimal in many SSA countries due to individual and health system-related challenges. Health system strengthening is vital to ensure the sustainability of HIV treatment programmes and the achievement of 95-95-95 targets by 2030.

Nicola Luigi Bragazzi,1– 4 Hicham Khabbache,5 Khalid Ouazizi,6 Driss Ait Ali,6 Hanane El Ghouat,6 Laila El Alami,6 Hisham Atwan,7 Ruba Tuma,8– 10 Nomy Dickman,10 Raymond Farah,10,11 Rola Khamisy-Farah9,10 1Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Parma, Italy; 2Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada; 3Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 4United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair, Health Anthropology Biosphere and Healing Systems, University of Genoa, Genoa, Italy; 5Director of the UNESCO Chair “Lifelong Learning Observatory” (UNESCO/UMSBA), Fez, Morocco; 6Department of Psychology, Faculty of Arts and Human Sciences Fès-Saïss, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 7Department of Internal Medicine, Kaplan Medical Centre, Hebrew University, Rehovot, Israel; 8Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Galilee, Israel; 9Clalit Health Services, Akko, Israel; 10Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; 11Department of Internal Medicine B, Ziv Medical Center, Safed, IsraelCorrespondence: Nicola Luigi Bragazzi, Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Via Volturno 39, Parma, 43125, Italy, Tel +39 0521 903121, Email nicolaluigi.bragazzi@unipr.itPurpose: Sex and Gender-Based Medicine (SGBM) addresses the influence of sex and gender on health and healthcare, emphasizing personalized care. Integrating SGBM into medical education is challenging. This study examines the implementation of an SGBM course in an Israeli university during the first year of the medical school.Methods: The course integrated lectures, group work, online gender studies resources, workshops, teacher training, and essential literature. The curriculum spanned pre-clinical and clinical aspects, featuring seven 90-minute sessions. Surveys assessed course structure, content, and lecturers using a 5-point Likert scale and qualitative feedback. Quantitative analysis involved descriptive statistics, and thematic analysis was used for qualitative data.Results: Of the 84 students surveyed, 35 (41.7%) responded to the first part, and 30 (35.7%) to the second. The SGBM course received high satisfaction with an average score of 3.63, surpassing other first-year courses (average 3.21). Students appreciated the supportive academic atmosphere (mean score 4.20) and diverse teaching methods (mean score 4.03), while the development of feminist thinking was less appreciated (average score 3.49). Lecturers received high ratings (average score 4.33). Qualitative feedback highlighted the value of group work, the significance of the subject matter, and the helpfulness of supplementary videos. Students requested more content on contemporary issues like gender transition and patient perspectives. The feminist medicine aspect was contentious, with students seeking better gender balance and scientific evidence.Conclusion: Introducing SGBM into the first-year curriculum yielded positive results with high student satisfaction for content and lecturers. An expanded course module is planned, to be assessed at the end of the next academic year.Keywords: sex- and gender-based medicine, medical education, medical training, curriculum integration

Abstract Background Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. Methods A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. Results Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. Conclusions Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings.

Abstract Given limited institutional resources, low-income populations often rely on social networks to improve their socioeconomic outcomes. However, it remains in question whether small-scale social interactions could affect large-scale economic inequalities in under-resourced contexts. Here, we leverage population-level data from one of the poorest South African settings to construct a large-scale, geographically defined, inter-household social network. Using a multilevel network model, we show that having social ties in close geographic proximity is associated with stable household asset conditions, while geographically distant ties correlate to changes in asset allocation. Notably, we find that localised network interactions are associated with an increase in wealth inequality at the regional level, demonstrating how macro-level inequality may arise from micro-level social processes. Our findings highlight the importance of understanding complex social connections underpinning inter-household resource dynamics, and raise the potential of large-scale social assistance programs to reduce disparities in resource-ownership by accounting for local social constraints.

Abstract Background Tuberculosis (TB), a leading cause of infectious death, is curable when patients complete a course of multi-drug treatment. Because entry into the TB treatment cascade usually relies on symptomatic individuals seeking care, little is known about linkage to care and completion of treatment in people with subclinical TB identified through community-based screening. Methods Participants of the Vukuzazi study, a community-based survey that provided TB screening in the rural uMkhanyakude district of KwaZulu-Natal from May 2018 – March 2020, who had a positive sputum (GeneXpert or Mtb culture, microbiologically-confirmed TB) or a chest x-ray consistent with active TB (radiologically-suggested TB) were referred to the public health system. Telephonic follow-up surveys were conducted from May 2021 – January 2023 to assess linkage to care and treatment status. Linked electronic TB register data was accessed. We analyzed the effect of baseline HIV and symptom status (by WHO 4-symptom screen) on the TB treatment cascade. Results Seventy percent (122/174) of people with microbiologically-confirmed TB completed the telephonic survey. In this group, 84% (103/122) were asymptomatic and 46% (56/122) were people living with HIV (PLWH). By self-report, 98% (119/122) attended a healthcare facility after screening, 94% (115/122) started TB treatment and 93% (113/122) completed treatment. Analysis of electronic TB register data confirmed that 67% (116/174) of eligible individuals started TB treatment. Neither symptom status nor HIV status affected linkage to care. Among people with radiologically-suggested TB, 48% (153/318) completed the telephonic survey, of which 80% (122/153) were asymptomatic and 52% (79/153) were PLWH. By self-report, 75% (114/153) attended a healthcare facility after screening, 16% (24/153) started TB treatment and 14% (22/153) completed treatment. Nine percent (28/318) of eligible individuals had TB register data confirming that they started treatment. Conclusions Despite high rates of subclinical TB, most people diagnosed with microbiologically-confirmed TB after community-based screening were willing to link to care and complete TB treatment. Lower rates of linkage to care in people with radiologically-suggested TB highlight the importance of streamlined care pathways for this group. Clearer guidelines for the management of people who screen positive during community-based TB screening are needed.

Abstract Public policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UK's role in international hunting trophy trade by analyzing CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora) trade data for 2000–2021 and 2015–2021. For CITES‐listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature (IUCN) Red List of Threatened Species to determine whether hunting designated as “trophy hunting” is (i) likely a major threat contributing to species being of elevated conservation concern, (ii) likely or possibly causing localized declines, or (iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Government's impact assessment of the bill. In 2000–2021 an estimated 3494 hunting trophies from 73 CITES‐listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), that is, individual animals. Imports involved 158.86 ± 66.53 (mean ± SD) trophies/year (115.83 ± 32.27 WOEs/year). In 2015–2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of eight species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options.

IntroductionApproximately 75% of caregivers providing unpaid care to family members or friends experience persistent pain. Simultaneously, individuals who require caregiving commonly experience pain. The inherent complexity of pain is enhanced by relationship dynamics of two closely tied individuals (i.e., caregiving dyad = caregivers and care recipients). Currently there are no proven pain interventions that target the caregiving dyad. Thus, the purpose of this pilot study was to assess the feasibility of a new behavioral multi-modal intervention, the Merging Yoga and self-management to develop Skills (MY-Skills) intervention.MethodsEach participant was part of a caregiving dyad and all participants had moderate to severe musculoskeletal pain, a score of ≥4 of 6 on the short mini-mental status exam, were ≥18 years old, sedentary, able to speak English, able to stand, and living at home. Participants were randomized to MY-Skills or the control group. MY-Skills was offered twice a week for eight weeks and each two-hour session included yoga and self-management education developed specifically for caregiving dyads experiencing persistent pain. MY-Skills was group based and developed as an in-person intervention. Due to Covid-19, the intervention was moved online and data are presented for in-person and online cohorts. Benchmarks for feasibility were set a priori, addressing: recruitment, attrition, attendance, safety, acceptability/satisfaction, and study completion.ResultsThirteen participants completed the in-person MY-Skills intervention (caregivers n = 7, care-receivers n = 6) and 18 individuals completed the online MY-Skills intervention (9 dyads). Most participants had pain for ≥10 years. Recruitment and attrition benchmarks for the in-person intervention were not met; yet they were met for the online version. In-person and online MY-Skills intervention attendance, safety, acceptability/satisfaction, and completion exceeded benchmark criteria.DiscussionThe MY-Skills intervention appears feasible and acceptable, however changes to recruitment criteria are necessary. Additional testing and larger sample sizes are required to test efficacy. Trial registrationClinicaltrials.gov, #NCT03440320.

Cisplatin, a commonly used chemotherapy drug, is well-established for its ototoxic effects, primarily attributed to the damage it inflicts on cochlear hair cells. However, its impact on the vestibular system remains inadequately understood. Here, we provide a comprehensive review of existing literature concerning cisplatin-induced vestibulotoxicity. Animal studies have shown that cisplatin induces a vestibular hair cell loss that is dose-dependent, with the severity of damage also varying according to the route of administration. Notably, intratympanic and systemic injections in animal models have manifested significant damage primarily to utricular hair cells, with a lesser degree of damage observed for the other vestibular end organs. The underlying mechanisms of cisplatin induced vestibular hair cell loss include apoptosis, oxidative stress, and inflammatory cytokines. Several protective agents, such as Pifithrin-α, DAPT, Ginkgolide B, and heat shock proteins, have demonstrated efficacy in inhibiting cisplatin-induced vestibular damage in preclinical studies. Human clinical findings indicate that cisplatin treatment can cause vestibular dysfunction, characterized by symptoms ranging from transient dizziness to persistent vertigo. Challenges in diagnosis, including the limited utilization of comprehensive vestibular testing for many patients, contribute to the variability in reported outcomes. Cisplatin-induced vestibulotoxicity is a significant complication of chemotherapy, necessitating further research to understand its mechanisms and to improve diagnosis and management, ultimately aiming to enhance the quality of life for cancer patients undergoing cisplatin therapy.

Introduction Linked administrative data are widely used in epidemiology to capture patient data across multiple databases. Linkage error rates, critical to measure linkage performance, are rarely reported due to difficulty in obtaining representative gold standard. We propose a training and validation approach for linkage procedures that yield unbiased performance estimates even with a non-representative gold standard. Methods We linked patient records from two non-deduplicated databases for HIV monitoring in South Africa, TIER.Net and NHLS laboratory database, using a network-based probabilistic linkage and deduplication approach. National IDs (gold standard) were available for a non-representative minority of records (10%). We calculated sensitivity (Sen, share of true matches identified by the algorithm) and positive predictive value (PPV, share of algorithm-identified matches that were true matches). We adjusted for bias due to informative missingness in National IDs using inverse probability weights to break the link between missingness and match probability. Results 111,755 record pairs were considered. National IDs were not missing completely at random. Match probabilities for National ID record pairs exhibited substantially less uncertainty (mid-range match probabilities), inflating Sen and PPV. Before bias correction, Sen and PPV were estimated at 97.0% and 97.8% respectively. After bias correction for missing National IDs, Sen and PPV were estimated at 95.7% and 96.6%. Failure to address this bias understated the overlinkage rate (100% - PPV) by 35% and the underlinkage rate (100% - Sen) by 30%. Conclusion Failure to adjust for informative missingness in the gold standard may lead to biased validation metrics and over/underconfidence in linked data.

Background HIV cohort data are crucial for understanding the effects of HIV infection and treatment. Linkage between HIV clinical and population records unlocks potential to understand the cause and consequences of social-economic factors on HIV-care seeking behaviors and mortality outcomes. We created HIV data infrastructure by linking HIV treatment records with routinely collected records. Methods We linked HIV cohort data(n=119,434) to Health and Demographic Surveillance(n=256,425), laboratory tests(n=617,314), clinic visits and hospital admissions(n=170,325) from KwaZulu-Natal, an HIV-endemic setting in rural South Africa. We used graph-based probabilistic record linkage algorithm to link the data for HIV patients accessing care at 17 clinics within the Hlabisa sub-district. Africa Health Research Institute (AHRI) has collected health and demographic surveillance data since 2000. AHRI has set up a hospital information system in the district to capture ICD-10 code admissions and discharges. Results From the 5% sample of 462,524 linkage clusters, the computed F-score was 0.88, sensitivity was 88% and positive predictive value was 91%. 38.5% of the patient ID clusters contained records linked across multiple databases. 36% of the HIV patient ID clusters contained records linked with laboratory tests. 19.5% of the HIV patient ID clusters contained data on demographic surveillance. 12.5% of the HIV patient ID clusters contained records linked with clinic visits and hospital admissions. 4% of patient IDs contained records across all four databases. Conclusion We have successfully created a cross-sectorial HIV cohort through probabilistic record linkage methods. The cohort provides a platform to answer policy-relevant questions.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Commonly used methods for both clinical diagnosis of SARS-CoV-2 infection and management of infected patients involve the detection of viral RNA, but the presence of infectious virus particles is unknown. Viability PCR (v-PCR) uses a photoreactive dye to bind non-infectious RNA, ideally resulting in the detection of RNA only from intact virions. This study aimed to develop and validate a rapid v-PCR assay for distinguishing intact and compromised SARS-CoV-2. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures with decreasing percentages of intact SARS-CoV-2 (from 100% to 0%) were prepared from SARS-CoV-2 virus stock and a clinical sample. Each sample was divided into a PMAxx-treated part and a non-PMAxx-treated part. Reverse transcription-PCR (RT-PCR) using an in-house developed SARS-CoV-2 viability assay was then applied to both sample sets. The difference in intact SARS-CoV-2 was determined by subtracting the cycle threshold (Ct) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of intact SARS-CoV-2 showed increasingly lower delta Ct values as the percentage of intact SARS-CoV-2 decreased, as expected. This relationship was observed in both high and low viral load samples prepared from cultured SARS-CoV-2 virus stock, as well as for a clinical sample prepared directly from a SARS-CoV-2 positive nasopharyngeal swab. In this study, a rapid v-PCR assay has been validated that can distinguish intact from compromised SARS-CoV-2. The presence of intact virus particles, as determined by v-PCR, may indicate SARS-CoV-2 infectiousness.IMPORTANCEThis study developed a novel method that can help determine whether someone who has been diagnosed with coronavirus disease 2019 (COVID-19) is still capable of spreading the virus to others. Current tests only detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, but cannot tell whether the particles are still intact and can thus infect cells. The researchers used a dye that selectively blocks the detection of damaged virions and free RNA. They showed that this viability PCR reliably distinguishes intact SARS-CoV-2 capable of infecting from damaged SARS-CoV-2 or free RNA in both cultured virus samples and a clinical sample. Being able to quickly assess contagiousness has important implications for contact tracing and safely ending isolation precautions. This viability PCR technique provides a simple way to obtain valuable information, beyond just positive or negative test results, about the actual risk someone poses of transmitting SARS-CoV-2 through the air or surfaces they come into contact with.

Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution. Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 μm. The preoperative endothelial cell density (ECD) was 2414 cells/mm2. During treatment, corneal thickness was 325 μm after epithelial debridement and 375 μm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 μm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 μm, the ECD was 1514 cells/mm2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 μm, just above the corneal endothelium. Conclusions and importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 μm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication.

Abstract Autophagy in eukaryotes functions to maintain homeostasis by degradation and recycling of long-lived and unwanted cellular materials. Autophagy plays important roles in pathogenicity of various fungal pathogens, suggesting that autophagy is a novel target for development of antifungal compounds. Here, we describe bioluminescence resonance energy transfer (BRET)-based high-throughput screening (HTS) strategy to identify compounds that inhibit fungal ATG4 cysteine protease-mediated cleavage of ATG8 that is critical for autophagosome formation. We identified ebselen (EB) and its analogs ebselen oxide (EO) and 2-(4-methylphenyl)−1,2-benzisothiazol-3(2H)-one (PT) as inhibitors of fungal pathogens Botrytis cinerea and Magnaporthe oryzae ATG4-mediated ATG8 processing. The EB and its analogs inhibit spore germination, hyphal development, and appressorium formation in Ascomycota pathogens, B. cinerea, M. oryzae, Sclerotinia sclerotiorum and Monilinia fructicola. Treatment with EB and its analogs significantly reduced fungal pathogenicity. Our findings provide molecular insights to develop the next generation of antifungal compounds by targeting autophagy in important fungal pathogens.

Nicola Luigi Bragazzi,1–4 Hicham Khabbache,5 Khalid Ouazizi,6 Driss Ait Ali,6 Hanane El Ghouat,6 Laila El Alami,6 Hisham Atwan,7 Ruba Tuma,8–10 Nomy Dickman,10 Raymond Farah,10,11 Rola Khamisy-Farah9,10 1Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Parma, Italy; 2Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada; 3Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 4United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair, Health Anthropology Biosphere and Healing Systems, University of Genoa, Genoa, Italy; 5Director of the UNESCO Chair “Lifelong Learning Observatory” (UNESCO/UMSBA), Fez, Morocco; 6Department of Psychology, Faculty of Arts and Human Sciences Fès-Saïss, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 7Department of Internal Medicine, Kaplan Medical Centre, Hebrew University, Rehovot, Israel; 8Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Galilee, Israel; 9Clalit Health Services, Akko, Israel; 10Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; 11Department of Internal Medicine B, Ziv Medical Center, Safed, IsraelCorrespondence: Nicola Luigi Bragazzi, Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Via Volturno 39, Parma, 43125, Italy, Tel +39 0521 903121, Email nicolaluigi.bragazzi@unipr.it

Oligo-deoxythymidine (oligo-dT) ligand-based affinity chromatography is a robust method for purifying mRNA drug substances within the manufacturing process of mRNA-based products, including vaccines and therapeutics. However, the conventional batch mode of operation for oligo-dT chromatography has certain drawbacks that reduce the productivity of this process. Here, we report a new continuous oligo-dT chromatography process for the purification of in vitro transcribed mRNA, which reduces losses, improves the efficiency of oligo-dT resin use, and intensifies the chromatography process. Furthermore, the quality by design (QbD) framework was used to establish a design space for the newly developed method. The optimization of process parameters (PPs), including salt type, salt concentration, load flow rate and mRNA load concentration both in batch and the continuous mode, achieved a greater than 90% yield (mRNA recovery) along with greater than 95% mRNA integrity and greater than 99% purity. The productivity of continuous chromatography was estimated to be 5.75-fold higher, and the operating cost was estimated 15% lower, when compared with batch chromatography. Moreover, the QbD framework was further used to map the relationship between critical quality attributes and key performance indicators as a function of critical process parameters and critical material attributes.

: Introduction: In South Africa, the HIV care cascade remains suboptimal. We investigated the impact of small conditional financial incentives (CFIs) and male‐targeted HIV‐specific decision‐support application (EPIC‐HIV) on the HIV care cascade. Methods: In 2018, in uMkhanyakude district, 45 communities were randomly assigned to one of four arms: (i) CFI for home‐based HIV testing and linkage to care within 6 weeks (R50 [US$3] food voucher each); (ii) EPIC‐HIV which are based on self‐determination theory; (iii) both CFI and EPIC‐HIV; and (iv) standard of care. EPIC‐HIV consisted of two components: EPIC‐HIV 1, provided to men through a tablet before home‐based HIV testing, and EPIC‐HIV 2, offered 1 month later to men who tested positive but had not yet linked to care. Linking HITS trial data to national antiretroviral treatment (ART) programme data and HIV surveillance programme data, we estimated HIV status awareness after the HITS trial implementation, ART status 3 month after the trial and viral load suppression 1 year later. Analysis included all known individuals living with HIV in the study area including those who did not participated in the HITS trial. Results: Among the 33,778 residents in the study area, 2763 men and 7266 women were identified as living with HIV by the end of the intervention period and included in the analysis. After the intervention, awareness of HIV‐positive status was higher in the CFI arms compared to non‐CFI arms (men: 793/908 [87.3%] vs. 1574/1855 [84.9%], RR = 1.03 [95% CI: 0.99−1.07]; women: 2259/2421 [93.3%] vs. 4439/4845 [91.6%], RR = 1.02 [95% CI: 1.00−1.04]). Three months after the intervention, no differences were found for linkage to ART between arms. One year after the intervention, only 1829 viral test results were retrieved. Viral suppression was higher but not significant in the EPIC‐HIV intervention arms among men (65/99 [65.7%] vs. 182/308 [59.1%], RR = 1.11 [95% CI: 0.88−1.40]). Conclusions: Small CFIs can contribute to achieve the first step of the HIV care cascade. However, neither CFIs nor EPIC‐HIV was sufficient to increase the number of people on ART. Additional evidence is needed to confirm the impact of EPIC‐HIV on viral suppression., INTRODUCTION Despite progress towards UNAIDS's 95‐95‐95, the number of people living with HIV (PLHIV) aware of their HIV status or on antiretroviral treatment (ART) remains insufficient in South Africa [1]. [...]

Abstract Strawberry or red leopards are a rare colour morph of leopard (Panthera pardus) characterised by spot markings that are red or brown instead of black, thought to be a result of a mutation in the tyrosinase‐related protein (TYRP1) gene. We report the first record of this phenotype on the African continent outside of South Africa, from Selous Game Reserve in southern Tanzania. One female leopard with strawberry colouration was documented out of 373 individual leopards (0.3%) identified through camera trap surveys conducted from 2020 to 2022 over a combined area of more than 4600 km2 in the Nyerere‐Selous landscape.

Abstract Introduction In South Africa, the HIV care cascade remains suboptimal. We investigated the impact of small conditional financial incentives (CFIs) and male‐targeted HIV‐specific decision‐support application (EPIC‐HIV) on the HIV care cascade. Methods In 2018, in uMkhanyakude district, 45 communities were randomly assigned to one of four arms: (i) CFI for home‐based HIV testing and linkage to care within 6 weeks (R50 [US$3] food voucher each); (ii) EPIC‐HIV which are based on self‐determination theory; (iii) both CFI and EPIC‐HIV; and (iv) standard of care. EPIC‐HIV consisted of two components: EPIC‐HIV 1, provided to men through a tablet before home‐based HIV testing, and EPIC‐HIV 2, offered 1 month later to men who tested positive but had not yet linked to care. Linking HITS trial data to national antiretroviral treatment (ART) programme data and HIV surveillance programme data, we estimated HIV status awareness after the HITS trial implementation, ART status 3 month after the trial and viral load suppression 1 year later. Analysis included all known individuals living with HIV in the study area including those who did not participated in the HITS trial. Results Among the 33,778 residents in the study area, 2763 men and 7266 women were identified as living with HIV by the end of the intervention period and included in the analysis. After the intervention, awareness of HIV‐positive status was higher in the CFI arms compared to non‐CFI arms (men: 793/908 [87.3%] vs. 1574/1855 [84.9%], RR = 1.03 [95% CI: 0.99−1.07]; women: 2259/2421 [93.3%] vs. 4439/4845 [91.6%], RR = 1.02 [95% CI: 1.00−1.04]). Three months after the intervention, no differences were found for linkage to ART between arms. One year after the intervention, only 1829 viral test results were retrieved. Viral suppression was higher but not significant in the EPIC‐HIV intervention arms among men (65/99 [65.7%] vs. 182/308 [59.1%], RR = 1.11 [95% CI: 0.88−1.40]). Conclusions Small CFIs can contribute to achieve the first step of the HIV care cascade. However, neither CFIs nor EPIC‐HIV was sufficient to increase the number of people on ART. Additional evidence is needed to confirm the impact of EPIC‐HIV on viral suppression.

Abstract Behavioral variation abounds in nature. This variation is important for adaptation and speciation, but its molecular basis remains elusive. Here, we use a hybrid zone between two subspecies of songbirds that differ in migration – an ecologically important and taxonomically widespread behavior---to gain insight into this topic. We measure gene expression in five brain regions. Differential expression between migratory states was dominated by circadian genes in all brain regions. The remaining patterns were largely brain-region specific. For example, expression differences between the subspecies that interact with migratory state likely help maintain reproductive isolation in this system and were documented in only three brain regions. Contrary to existing work on regulatory mechanisms underlying species-specific traits, two lines of evidence suggest that trans- (vs. cis) regulatory changes underlie these patterns – no evidence for allele-specific expression in hybrids and minimal associations between genomic differentiation and expression differences. Additional work with hybrids shows expression levels were often distinct (transgressive) from parental forms. Behavioral contrasts and functional enrichment analyses allowed us to connect these patterns to mitonuclear incompatibilities and compensatory responses to stress that could exacerbate selection on hybrids and contribute to speciation.