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The demand for honey and pollination services has continued to grow in many countries worldwide, including New Zealand. This has influenced changes in the demographics of the managed population of honey bees (Apis mellifera). We examined historical data to describe how the apicultural demographics in New Zealand have changed temporally and geographically in the four decades to 2020. We also describe trends in honey production and the economic value of pure honey exported from New Zealand between 2000 and 2020. Our findings suggest that commercial apiculture has been key to the intensification of beekeeping in New Zealand during the study period. This is supported by evidence showing pronounced expansion of beekeeping operations among those with more than 1,000 colonies. The intensification has resulted in the density of apiaries increasing threefold across New Zealand during the four decades. While higher numbers of colonies per area produced higher volumes of honey, there was no corresponding improvement in production efficiency. Honey yields per apiary or colony, as indicators of production efficiency, appear to decline from the mid-2000s. The volume of pure honey export increased over 40-fold, a magnitude approximately ten times higher than that of production increase. This reflects a substantial increase in returns from honey exports, mostly driven by the price of mānuka honey. Our findings add to a pool of information to support evidence-based decision making to enhance honey bee health and develop the apicultural industry in New Zealand.

The aquatic and terrestrial clades of species of Trypanosoma could provide insight into the evolutionary history of the genus, as well as complementary information for biomedical studies of medically and economically important species of Trypanosoma. The ecological interactions and phylogeny of aquatic trypanosomes are currently not well-understood, mostly due to their complex life cycles and a deficiency of data. The species of Trypanosoma from African anuran hosts are of the least understood taxa in the genus. Trypanosomes were collected from South African frogs and subjected to morphological and phylogenetic analyses. This study redescribes Trypanosoma (Trypanosoma) nelspruitense Laveran, 1904 and Trypanosoma (Haematomonas) grandicolor Pienaar, 1962, with morphological and molecular data. The present study aims to create a platform for further future research on African anuran trypanosomes.

Although mice are social animals, individual housing is sometimes requested after surgery. We questioned whether pair-housing mice after surgery resulted in greater trauma to the surgical site as compared with single housing. We further evaluated the effect of individual housing after surgery on the wellbeing of mice that had previously been pair-housed. Female C57Bl/6 mice (age, 6 to 8 wk) were housed as follows: group A, individually housed before and after surgery (n = 10; all 10 mice underwent surgery); group B, pair-housed before surgery but individually housed after surgery (n = 10; all 10 mice received surgery); group C, pair-housed before and after surgery (n = 20; 10 mice underwent surgery but their cage mates did not); and group D, pair-housed before and after surgery (n = 10; all 10 mice underwent surgery). Dependent variables were body weight, body condition, grimace based on real-time scoring, nest building, time to incorporate into nest test (TINT) score, wound trauma score, and missing wound clips. Weight was significantly different between groups A and C both before and after surgery. Mean nest building scores were significantly higher for pair-housed (groups C and D) than for individually housed mice (groups A and B) after surgery while TINT scores were significantly higher for these same groups both before and after surgery. Mean values for body condition, grimace score, wound score, and number of wound clips missing did not differ significantly between any groups either before or after surgery. Taken together, these results suggest that pair housing mice after surgery benefited their wellbeing but did not increase trauma to the surgical incision site or disturb wound clips as compared with individually housed mice. Furthermore, separating previously pair-housed mice (group B) did not affect these measures as compared with individually housed mice (Group A) either before or after surgery.

Bernard J Crespi,1 Susan F Evans2 1Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada; 2Adelaide Medical School, School of Medicine, University of Adelaide, Adelaide, South Australia, AustraliaCorrespondence: Bernard J Crespi, Email crespi@sfu.caAbstract: Endometriosis is a polygenic, estrogen-dependent, inflammatory disorder of uncertain aetiology associated with pain, infertility and reduced quality of life. While the positive association between endometriosis and estrogen is established, a suite of recent studies has demonstrated an inverse association between the presence of endometriosis lesions and levels of testosterone both prenatally and postnatally. The following narrative review provides new insights into the roles of testosterone in the aetiology, diagnosis, and management of endometriosis and associated symptoms, especially pain. A relatively short anogenital distance (AGD) is indicative of lower levels of testosterone during fetal development. A shorter AGD has recently been correlated with both a higher risk of developing endometriosis in adult life, and with known correlates of endometriosis including earlier onset of reproductive cycling, lower ovarian follicle number, lower postnatal testosterone, and premature ovarian insufficiency. During adult life, lower levels of testosterone are positively associated with key comorbidities of endometriosis, including days per month of pelvic pain and increased pain sensitivity. Biochemically, lower levels of testosterone are associated with higher levels of pro-inflammatory IL-1β and lower levels of β-endorphin. In rodents, prenatal administration of testosterone to females reduces their pain sensitivity in adulthood. The emerging convergent links of endometriosis with low prenatal and postnatal testosterone provide evidence of a centrally mediated effect beginning in early prenatal development, and persisting through adult life, with notable effects on pain sensitivity. They generate a novel conceptual framework for understanding, studying and treating this disorder, whereby endometriosis is mediated by a combination of high estrogen in endometrial tissue with low systemic and ovarian testosterone.Keywords: endometriosis, pain, testosterone, anogenital distance, fetal development

We report here a dual-ELISA method to measure Malaria biomarkers concurrently in the same aliquot of blood sample. A correlation between the parasite numbers and ELISA values determined and the figures were used to establish a standard graph. Thick blood smears prepared from spiked blood samples were also Giemsa stained and parasite density determined by microscopy (It was thereby possible to undertake an objective comparison between lactate dehydrogenase and histidine- rich- proteins levels assessed by ELISA and parasite density determined by microscopy from the same spiked aliquot). The presence of lactate dehydrogenase and histidine- rich- proteins is localized and visualized by fluorescent antibody techniques. Twenty-two patient blood samples were retrospectively analyzed for the levels of pLDH and HRPs and their level was quantified in each blood sample. Fresh blood samples from malaria patients seeking care at a healthcare facility in an endemic area were then collected and separated into plasma and infected red blood cells and parasitemia levels determined. The biomarkers which were released into plasma from circulating and sequestered parasites provide a more accurate picture and indicate degree of disease severity. Since lactate dehydrogenase is known to have a short half-life compared to the histidine-rich proteins, its plasma level is believed to reflect on the number of metabolically active parasites more accurately and more reliable indicator of clinical outcome. In contrast, histidine -rich proteins accumulate in plasma and measurable levels persist long after patients have been treated and parasites cleared from their system. Best practice may now call for a pre-eminent role for microscopy and PCR in plasmodium species confirmation, a continued role for newer histidine-rich protein assays in epidemiological studies and control, and the preferential use of parasite lactate dehydrogenase in the clinical management of the disease. Data presented here from spiked blood samples as well as naturally infected patient samples provide evidence that by splitting whole blood samples into RBC-pellet and plasma, determination of parasite biomarkers in split sample fractions gives a true picture of malaria parasites present in humans and this may improve the accuracy of models that attempt to predict parasite burdens more accurately, and so clinical correlations.

Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis. Although these scores inform the probability of developing a tumor, it remains unknown how germline risk influences the tumor molecular evolution. We cultivated a cohort of 1250 localized European-descent patients with germline and somatic DNA profiling. Men of European descent with higher genetic risk were diagnosed earlier and had less genomic instability and fewer driver genes mutated. Higher genetic risk was associated with better outcome. These data imply a polygenic “two-hit” model where germline risk reduces the number of somatic alterations required for tumorigenesis. These findings support further clinical studies of polygenic risk scores as inexpensive and minimally invasive adjuncts to standard risk stratification. Further studies are required to interrogate generalizability to more ancestrally and clinically diverse populations.

Organ preservation for muscle-invasive bladder cancer (MIBC) may use trimodality therapy. This includes transurethral resection followed by radiation therapy. Radiosensitization has become one of the standard of care approaches for MIBC with high rates of local disease control and overall survival. The goal of organ preservation is to treat MIBC while preserving a well-functioning natural bladder. Debate remains over the best way to optimize radiation therapy in bladder cancer. In MIBC the role of partial cystectomy has been utilized in smaller solitary tumors with adequate local control and good urinary function. As radiation therapy techniques improve and modernize, smaller radiation volumes to a partial bladder may play an increasing role as we utilize imaging techniques coupled with adaptive radiation therapy planning and other techniques such as brachytherapy. In this review, we explore the use of brachytherapy and partial bladder fields of external beam radiation therapy in the treatment of MIBC.

Rust fungi (Pucciniales) are a diverse group of plant pathogens in natural and agricultural systems. They pose ongoing threats to the diversity of native flora and cause annual crop yield losses. Agricultural rusts are predominantly managed with fungicides and breeding for resistance, but new control strategies are needed on non-agricultural plants and in fragile ecosystems. RNA interference (RNAi) induced by exogenous double-stranded RNA (dsRNA) has promise as a sustainable approach for managing plant-pathogenic fungi, including rust fungi. We investigated the mechanisms and impact of exogenous dsRNA on rust fungi through in vitro and whole-plant assays using two species as models, Austropuccinia psidii (the cause of myrtle rust) and Coleosporium plumeriae (the cause of frangipani rust). In vitro, dsRNA either associates externally or is internalized by urediniospores during the early stages of germination. The impact of dsRNA on rust infection architecture was examined on artificial leaf surfaces. dsRNA targeting predicted essential genes significantly reduced germination and inhibited development of infection structures, namely appressoria and penetration pegs. Exogenous dsRNA sprayed onto 1-year-old trees significantly reduced myrtle rust symptoms. Furthermore, we used comparative genomics to assess the wide-scale amenability of dsRNA to control rust fungi. We sequenced genomes of six species of rust fungi, including three new families (Araucariomyceaceae, Phragmidiaceae, and Skierkaceae) and identified key genes of the RNAi pathway across 15 species in eight families of Pucciniales. Together, these findings indicate that dsRNA targeting essential genes has potential for broad-use management of rust fungi across natural and agricultural systems.

Previous atrial fibrillation screening trials have highlighted the need for more targeted approaches. We did a pragmatic study to evaluate the effectiveness of an artificial intelligence (AI) algorithm-guided targeted screening approach for identifying previously unrecognised atrial fibrillation.For this non-randomised interventional trial, we prospectively recruited patients with stroke risk factors but with no known atrial fibrillation who had an electrocardiogram (ECG) done in routine practice. Participants wore a continuous ambulatory heart rhythm monitor for up to 30 days, with the data transmitted in near real time through a cellular connection. The AI algorithm was applied to the ECGs to divide patients into high-risk or low-risk groups. The primary outcome was newly diagnosed atrial fibrillation. In a secondary analysis, trial participants were propensity-score matched (1:1) to individuals from the eligible but unenrolled population who served as real-world controls. This study is registered with ClinicalTrials.gov, NCT04208971.1003 patients with a mean age of 74 years (SD 8·8) from 40 US states completed the study. Over a mean 22·3 days of continuous monitoring, atrial fibrillation was detected in six (1·6%) of 370 patients with low risk and 48 (7·6%) of 633 with high risk (odds ratio 4·98, 95% CI 2·11-11·75, p=0·0002). Compared with usual care, AI-guided screening was associated with increased detection of atrial fibrillation (high-risk group: 3·6% [95% CI 2·3-5·4] with usual care vs 10·6% [8·3-13·2] with AI-guided screening, p0·0001; low-risk group: 0·9% vs 2·4%, p=0·12) over a median follow-up of 9·9 months (IQR 7·1-11·0).An AI-guided targeted screening approach that leverages existing clinical data increased the yield for atrial fibrillation detection and could improve the effectiveness of atrial fibrillation screening.Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery.

Understanding the natural history of coronary artery atherosclerosis is necessary to determine prognosis and prescribe effective therapies. Traditional management of coronary artery disease has focused on the treatment of flow-limiting anatomical obstructions that lead to ischaemia. In most scenarios, revascularization of these atherosclerotic plaques has not substantially improved freedom from death or myocardial infarction, questioning the utility of contemporary revascularization strategies to improve prognosis. Advances in non-invasive and invasive imaging techniques have helped to identify the characteristics of obstructive and non-obstructive plaques that are precursors for plaque progression and future acute coronary syndromes as well as cardiac death. These 'vulnerable plaques' develop as a consequence of systemic inflammation and are prone to inducing thrombosis. Vulnerable plaques most commonly have a large plaque burden with a well-formed necrotic core and thin fibrous cap and are metabolically active. Perivascular adipose tissue might, in some patients, be used as a surrogate for coronary inflammation and predict future risk of adverse cardiac events. Vulnerable plaques can be identified in their quiescent state, offering the potential for therapeutic passivation. In this Review, we describe the biological and compositional features of vulnerable plaques, the non-invasive and invasive diagnostic modalities to characterize vulnerable plaques, the prognostic utility of identifying vulnerable plaques, and the future studies needed to explore the value of intensified pharmacological and focal treatments of vulnerable plaques.

RNA interference is triggered in plants by the exogenous application of double-stranded RNA or small interfering RNA (siRNA) to silence the expression of target genes. This approach can potentially provide insights into metabolic pathways and gene function and afford plant protection against viruses and other plant pathogens. However, the effective delivery of biomolecules such as siRNA into plant cells is difficult because of the unique barrier imposed by the plant cell wall. Here, we demonstrate that 40-nm layered double hydroxide (LDH) nanoparticles are rapidly taken up by intact Nicotiana benthamiana leaf cells and by chloroplasts, following their application via infiltration. We also describe the distribution of infiltrated LDH nanoparticles in leaves and demonstrate their translocation through the apoplast and vasculature system. Furthermore, we show that 40-nm LDH nanoparticles can greatly enhance the internalization of nucleic acids by N. benthamiana leaf cells to facilitate siRNA-mediated downregulation of targeted transgene mRNA by >70% within 1 day of exogenous application. Together, our results show that 40-nm LDH nanoparticle is an effective platform for delivery of siRNA into intact plant leaf cells.

To assess long-term outcomes with robotic versus laparoscopic/thoracoscopic and open surgery for colorectal, urologic, endometrial, cervical, and thoracic cancers.Minimally invasive surgery provides perioperative benefits and similar oncological outcomes compared with open surgery. Recent robotic surgery data have questioned long-term benefits.A systematic review and meta-analysis of cancer outcomes based on surgical approach was conducted based on PRISMA guidelines using Pubmed, Scopus, and Embase. HRs for recurrence, disease-free survival (DFS), and overall survival (OS) were extracted/estimated using a hierarchical decision-tree and pooled in RevMan 5.4 using inverse-variance fixed effect (heterogeneity non-significant) or random effect models.Of 31,204 references, 199 were included (7 randomized, 23 database, 15 prospective, 154 retrospective studies)-157,876 robotic, 68,007 laparoscopic/thoracoscopic, and 234,649 open cases. Cervical cancer: OS and DFS were similar between robotic and laparoscopic (1.01[0.56, 1.80], P=0.98) or open (1.18[0.99, 1.41], P=0.06) surgery; two papers reported less recurrence with open surgery (2.30[1.32, 4.01], P=0.003). Endometrial cancer: the only significant result favored robotic over open surgery (OS; 0.77[0.71, 0.83], P0.001). Lobectomy: DFS favored robotic over thoracoscopic surgery (0.74[0.59, 0.93], P=0.009); OS favored robotic over open surgery (0.93[0.87, 1.00], P=0.04). Prostatectomy: recurrence was less with robotic versus laparoscopic surgery (0.77[0.68, 0.87], P0.0001); OS favored robotic over open surgery (0.78[0.72, 0.85], P0.0001). Low-anterior resection: OS significantly favored robotic over laparoscopic (0.76[0.63, 0.91], P=0.004) and open surgery (0.83[0.74, 0.93], P=0.001).Long-term outcomes were similar for robotic versus laparoscopic/thoracoscopic and open surgery, with no safety signal or indication requiring further research (PROSPERO Reg#CRD42021240519).

Existing ergonomic assessment tools have been designed for routine and structured work making their use in informal work setting challenging due to the high variability in tasks performed by informal workers. The Ergonomic Assessment tool for Unstructured Work (EAUW) was developed by Acquah and colleagues to address this challenge. The tool is efficient and has good inter-observer reliability, but little information is known about its other psychometric properties. This paper assesses the reliability and validity of EAUW. Criterion validity was determined by comparing the EAUW with existing tools for a selected number of e-waste recycling tasks. Intra-observer reliability was determined by comparing observations from the same assessor 5 days apart. Results indicated a high intra-observer agreement for all exposure variables. Compared to existing tools which provide a snapshot of ergonomic exposures, the EAUW provides a more detailed estimate of work exposures between- and within-workers across time.

Independent mobility is crucial for healthy aging. Although there are anticipated differences between older adults with earlier-in-life (EL) versus later-in-life (LL) incidence of mobility disability, the degree to which incidence periods impact performance within environments is unknown. While current evaluation methods rely heavily on subjective ratings, historically excluded populations are prone to underrepresent their own challenges. This paper describes an experiment comparing the assumed, perceived, and effective performance of manual wheelchair movement tasks to examine differences between EL and LL groups. Preliminary results found higher muscular exertion in the LL group compared to the EL group for similar movements, particularly in the anterior and posterior deltoid muscles. There was a greater mismatch between the assumed and perceived mental and physical demand for the LL group. For both groups, results suggest poorer mental models for moderate-difficulty tasks compared to high-difficulty tasks, suggesting a need for increased perceptual feedback within moderate-difficulty environments.

This mixed-methods survey study aims to describe the effects of the COVID-19 pandemic on the mental health of a sample of 571 children and adolescent seeking psychiatric emergency care. The study was conducted from July to October 2020 at a large Midwestern academic center. Among the respondents, there were significant increases in mental health symptoms attributed to the COVID-19 pandemic, including anxiety (71% of respondents), depression (66%), suicidal thoughts or behaviors (45%), and aggression (31%). There were significant differences in reported increases in symptoms by age and gender. In addition, 38% of participants reported that the pandemic led to a change or closure of their health care treatment, including mental health providers, with 22% reporting that reduced treatment access led to their emergency visit. Further research is indicated to assess other, more diverse populations, as well as the longer-term mental health impacts of the pandemic.

BACKGROUND: Postoperative atrial fibrillation (AF) after non-cardiac surgery confers increased risks of ischemic stroke and transient ischemic attack (TIA). How outcomes for postoperative AF after non-cardiac surgery compare to AF occurring outside of the operative setting is unknown. OBJECTIVE: To compare the risks of ischemic stroke or TIA and other outcomes in patients with postoperative AF compared to those with incident AF not associated with surgery. DESIGN: Cohort study. SETTING: Olmsted County, MN. PARTICIPANTS: Patients with incident AF between 2000 and 2013. MEASUREMENTS: Patients were categorized as AF occurring within 30 days of a non-cardiac surgery (postoperative AF) and those with AF unrelated to surgery (non-operative AF). RESULTS: Of 4,231 patients with incident AF, 550 (13%) had postoperative AF as their first-ever documented AF presentation. Over a mean follow-up of 6.3 years, 486 patients experienced an ischemic stroke or TIA, 2,462 had subsequent AF, and 2,565 deaths occurred. The risk of stroke or TIA was similar between those with postoperative AF and non-operative AF (absolute risk difference (ARD) at 5 years, 0.1% [−2.9%–3.1%]; hazard ratio (HR), 1.01 [0.77–1.32]). A lower risk of subsequent AF was observed for patients with postoperative AF (ARD at 5 years, −13.4% [−17.8%- −9.0%]; HR, 0.68 [0.60–0.77]. Finally, no difference was observed for cardiovascular death or all-cause death between patients with postoperative AF and non-operative AF. LIMITATIONS: The population consisted predominantly of whites; caution should be used extrapolating the results to more racially diverse populations. CONCLUSIONS: Postoperative AF after non-cardiac surgery is associated with similar risk of thromboembolism compared to non-operative AF. Our findings have potentially important implications for the early post-surgical and subsequent management of postoperative AF.

Little is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis.All patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors.Of 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P .01)-in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P .01)-was associated with increased risk of recurrence.One-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.

Atrial fibrillation (AF) is the most common arrhythmia among patients with heart failure (HF), and HF is the most common cause of death for patients presenting with clinical AF. AF is frequently associated with pathological atrial myocardial dysfunction and remodeling, a triad that has been called atrial myopathy. AF can be the cause or consequence of clinical HF, and the directionality varies between individual patients and across the spectrum of HF. Although initial trials suggested no advantage for a systematic rhythm control strategy in HF with reduced ejection fraction, recent data suggest that select patients may benefit from attempts to maintain sinus rhythm with catheter ablation. Preliminary data also show a close relationship among AF, left atrial myopathy, mitral regurgitation, and HF with preserved ejection, with potential clinical benefits to catheter ablation therapy. The modern management of AF in HF also requires consideration of the degree of atrial myopathy and chronicity of AF, in addition to the pathogenesis and phenotype of the underlying left ventricular HF. In this review, we summarize the contemporary management of AF and provide practical guidance and areas in need of future investigation.

„Fenomenologia: natura, znaczenie, ograniczenia” to przekład publikacji Bernarda J. F. Lonergana pt. „Phenomenology” nature, significance, limitations”. Tenże dwunasty wykład kanadyjskiego filozofia o fenomenologii traktuje o jej definicji, przedmiocie, naturze, znaczeniu i zasługach oraz związkach z innymi naukami. Wprowadza czytelnika w główne koncepcje tej szkoły filozoficznej i zapoznaje z autorami, dla których ten sposób myślenia jest charakterystyczny. Filozof w szczególności zwraca uwagę na to, iż jest to metoda badań, w której istotną rolę odgrywa wgląd (insight). Warto zauważyć, że kategoria wglądu w epistemologii Bernarda J. F. Lonergana (1904–1984) — XX-wiecznego myśliciela i księdza filozofującego na pograniczu fenomenologii, tomizmu i hermeneutyki — jest kluczowa. Przekładu dokonała Dominika Dziurosz-Serafinowicz.

People with HIV (PWH) have persistently elevated levels of inflammation and immune activation despite suppressive antiretroviral therapy (ART), with specific biomarkers showing associations with non-AIDS-defining morbidities and mortality. We investigated the potential role of the HIV-specific adaptive immune response, which also persists under ART, in driving levels of these clinically relevant biomarkers.Cohort-based study.HIV-specific IFN-γ-producing T-cell responses and antibody concentrations were measured in blood at study entry in the ACTG A5321 cohort, following a median of 7 years of suppressive ART. HIV persistence measures including cell-associated (CA)-DNA, CA-RNA, and plasma HIV RNA (single-copy assay) were also assessed at study entry. Plasma inflammatory biomarkers and T-cell activation and cycling were measured at a pre-ART time point and at study entry.Neither the magnitudes of HIV-specific T-cell responses nor HIV antibody levels were correlated with levels of the inflammatory or immune activation biomarkers, including hs-CRP, IL-6, neopterin, sCD14, sCD163, TNF-α, %CD38 + HLA-DR + CD8 + and CD4 + cells, and %Ki67 + CD8 + and CD4 + cells - including after adjustment for pre-ART biomarker level. Plasma HIV RNA levels were modestly correlated with CD8 + T-cell activation ( r = 0.25, P = 0.027), but other HIV persistence parameters were not associated with these biomarkers. In mediation analysis, relationships between HIV persistence parameters and inflammatory biomarkers were not influenced by either HIV-specific T-cell responses or antibody levels.Adaptive HIV-specific immune responses do not appear to contribute to the elevated inflammatory and immune activation profile in persons on long-term ART.

Large commercial sentiment analysis tools are often deployed in software engineering due to their ease of use. However, it is not known how accurate these tools are, and whether the sentiment ratings given by one tool agree with those given by another tool. We use two datasets - (1) NEWS consisting of 5,880 news stories and 60K comments from four social media platforms: Twitter, Instagram, YouTube, and Facebook; and (2) IMDB consisting of 7,500 positive and 7,500 negative movie reviews - to investigate the agreement and bias of four widely used sentiment analysis (SA) tools: Microsoft Azure (MS), IBM Watson, Google Cloud, and Amazon Web Services (AWS). We find that the four tools assign the same sentiment on less than half (48.1%) of the analyzed content. We also find that AWS exhibits neutrality bias in both datasets, Google exhibits bi-polarity bias in the NEWS dataset but neutrality bias in the IMDB dataset, and IBM and MS exhibit no clear bias in the NEWS dataset but have bi-polarity bias in the IMDB dataset. Overall, IBM has the highest accuracy relative to the known ground truth in the IMDB dataset. Findings indicate that psycholinguistic features - especially affect, tone, and use of adjectives - explain why the tools disagree. Engineers are urged caution when implementing SA tools for applications, as the tool selection affects the obtained sentiment labels.

Artificial intelligence, particularly machine learning, carries high potential to automatically detect customers’ pain points, which is a particular concern the customer expresses that the company can address. However, unstructured data scattered across social media make detection a nontrivial task. Thus, to help firms gain deeper insights into customers’ pain points, the authors experiment with and evaluate the performance of various machine learning models to automatically detect pain points and pain point types for enhanced customer insights. The data consist of 4.2 million user-generated tweets targeting 20 global brands from five separate industries. Among the models they train, neural networks show the best performance at overall pain point detection, with an accuracy of 85% (F1 score = .80). The best model for detecting five specific pain points was RoBERTa 100 samples using SYNONYM augmentation. This study adds another foundational building block of machine learning research in marketing academia through the application and comparative evaluation of machine learning models for natural language–based content identification and classification. In addition, the authors suggest that firms use pain point profiling, a technique for applying subclasses to the identified pain point messages to gain a deeper understanding of their customers’ concerns.

Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission.

Although the effect of hyperparameters on algorithmic outputs is well known in machine learning, the effects of hyperparameters on information systems that produce user or customer segments are relatively unexplored. This research investigates the effect of varying the number of user segments on the personification of user engagement data in a real analytics information system, employing the concept of persona. We increment the number of personas from 5 to 15 for a total of 330 personas and 33 persona generations. We then examine the effect of changing the hyperparameter on the gender, age, nationality, and combined gender-age-nationality representation of the user population. The results show that despite using the same data and algorithm, varying the number of personas strongly biases the information system’s personification of the user population. The hyperparameter selection for the 990 total personas results in an average deviation of 54.5% for gender, 42.9% for age, 28.9% for nationality, and 40.5% for gender-age-nationality. A repeated analysis of two other organizations shows similar results for all attributes. The deviation occurred for all organizations on all platforms for all attributes, as high as 90.9% in some cases. The results imply that decision makers using analytics information systems should be aware of the effect of hyperparameters on the set of user or customer segments they are exposed to. Organizations looking to effectively use persona analytics systems must be wary that altering the number of personas could substantially change the results, leading to drastically different interpretations about the actual user base.

0.AbstractEssential tremor (ET) is a neurological disorder characterized by involuntary oscillations of the limbs. Previous studies have hypothesized that ET was a cerebellar disorder and reported impairments in motor adaptation. However, recent advances have highlighted that motor adaptation involved several components linked to anticipation and control, all dependent on cerebellum, and the specific alteration of adaptation of ET has not been identified. To address this question we investigated behavioural markers of adaptation in ET patients (n=20) and age-matched healthy volunteers (n=20) in saccadic and upper limb adaptation tasks, probing compensation for target jumps and for velocity-dependent force fields, respectively. We found that both groups adapted their movements to the novel contexts, however, ET patients adapted to a lesser extent compared to healthy volunteers. Importantly, we decomposed movements into components linked to anticipation, preserved here, and real-time execution, which were responsible for the adaptation deficit. Altogether, our results suggest that execution deficits may be a specific functional consequence of the alteration of neural pathways associated with ET.Significance StatementWe tested Essential Tremor patients’ adaptation abilities in classical tasks including saccadic adaptation to target jumps and reaching adaptation to force field disturbances. Patients’ adaptation was present but impaired in both tasks. Interestingly, the deficits were mainly present during movement execution, while the anticipatory components of movements were similar to healthy volunteers. These findings reinforce the hypothesis of a cerebellar origin for essential tremor and details the motor adaptation impairments previously found in this disorder.

New Zealand is a remote country in the South Pacific Ocean. The isolation and relatively late arrival of humans into New Zealand has meant there is a recorded history of the introduction of domestic species. Honey bees (Apis mellifera) were introduced to New Zealand in 1839, and the disease American foulbrood was subsequently found in the 1870s. Paenibacillus larvae, the causative agent of American foulbrood, has been genome sequenced in other countries. We sequenced the genomes of P. larvae obtained from 164 New Zealand apiaries where American foulbrood was identified in symptomatic hives during visual inspection. Multi-locus sequencing typing (MLST) revealed the dominant sequence type to be ST18, with this clonal cluster accounting for 90.2% of isolates. Only two other sequence types (with variants) were identified, ST5 and ST23. ST23 was only observed in the Otago area, whereas ST5 was limited to two geographically non-contiguous areas. The sequence types are all from the enterobacterial repetitive intergenic consensus I (ERIC I) genogroup. The ST18 and ST5 from New Zealand and international P. larvae all clustered by sequence type. Based on core genome MLST and SNP analysis, localized regional clusters were observed within New Zealand, but some closely related genomes were also geographically dispersed, presumably due to hive movements by beekeepers.

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study.

Remote-sensing analysis of high-resolution satellite imagery of modern carbonate platforms in the Celebes Sea, east of Sabah, Borneo, Malaysia, was used to map geomorphology and sediment. Unsupervised classification of satellite images was interpreted in the context of environmental facies of seven isolated carbonate platforms and calibrated using analyses of surface sediments. In total, 140 sediment samples were collected and analyzed for grain-size and sorting. The grain-size analysis showed that sediment varied among the geomorphic elements, which included island, island/volcano, reef complex, carbonate sand shoal, grass-covered sand shoal, shallow lagoon, and deep lagoon. To generate carbonate sediment texture maps, the proportion of mud and the grain-size attributes (mean grain size and sorting) of each sediment sample provided a basis to classify samples into rock-equivalent textures. Integration of remote-sensing, field, and sedimentological data provided a means to characterize texture distribution maps and depositional facies maps. These maps suggest that mudstone to wackestone occurs mainly in the deep lagoon; wackestone to packstone is dominant in the shallow lagoon; the carbonate sand shoal is characterized by packstone to grainstone; and the reef complex is made up of boundstone to rudstone. These results facilitate estimates of the proportions of potential reservoirs on these platforms and the heterogeneity in facies distribution, based on the size of various recent carbonate platforms. Diagenesis notwithstanding, ancient analogs indicate the Selakan and Maiga platforms could be potential reservoirs, whereas the Selakan and Gaya platforms display more facies classes and represent poor potential reservoirs.

PDF file 65K, Primers used in assessment of RINT1 transcripts

PDF file 199K, RINT1 c.1334-5delA, c.1334-1_1335delGTT minigene assay

PDF file 69K, Distribution of cases and controls included in the analysis, by study center and ethnic group

Distribution of the ratio of variant allele frequency to ctDNA fraction of mutations and rearrangements in the AR gene.

Purpose:Comprehensive genomic profiling (CGP) is of increasing value for patients with metastatic castration-resistant prostate cancer (mCRPC). mCRPC tends to metastasize to bone, making tissue biopsies challenging to obtain. We hypothesized CGP of cell-free circulating tumor DNA (ctDNA) could offer a minimally invasive alternative to detect targetable genomic alterations (GA) that inform clinical care.Experimental Design:Using plasma from 3,334 patients with mCRPC (including 1,674 screening samples from TRITON2/3), we evaluated the landscape of GAs detected in ctDNA and assessed concordance with tissue-based CGP.Results:A total of 3,129 patients (94%) had detectable ctDNA with a median ctDNA fraction of 7.5%; BRCA1/2 was mutated in 295 (8.8%). In concordance analysis, 72 of 837 patients had BRCA1/2 mutations detected in tissue, 67 (93%) of which were also identified using ctDNA, including 100% of predicted germline variants. ctDNA harbored some BRCA1/2 alterations not identified by tissue testing, and ctDNA was enriched in therapy resistance alterations, as well as possible clonal hematopoiesis mutations (e.g., in ATM and CHEK2). Potential androgen receptor resistance alterations were detected in 940 of 2,213 patients (42%), including amplifications, polyclonal and compound mutations, rearrangements, and novel deletions in exon 8.Conclusions:Genomic analysis of ctDNA from patients with mCRPC recapitulates the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 mutations, but more acquired resistance alterations detected in ctDNA. CGP of ctDNA is a compelling clinical complement to tissue CGP, with reflex to tissue CGP if negative for actionable variants.See related commentary by Hawkey and Armstrong, p. 2961

Positive percent agreement (PPA) between patient-matched cancer tissue and liquid biopsies.

Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large “test” set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.

L. reuteri dietary enrichment protects the F1 progeny of NWD-fed mothers from transgenerational cancer. Pulmonary adenocarcinoma, hepatocellular carcinoma and mesenteric lymph node lymphoma in the children of mothers consuming NWD are shown in the left column. Compare with normal lung, liver and mesenteric lymph node histology from mice of similar descend that were also treated with L. reuteri.

Nutritional profile of special diets fed to mice.

Control and NWD-treated mice cluster separately by microbiota. NWD-treated mice carry fewer Bacteroidetes in general than their control diet-fed counterparts. Overall, there is a shift towards higher abundance of OTUs from the Firmicutes phyla and decrease in OTUs from the Bacteroidetes phyla in mice treated with NWD. These data are consistent with previous findings of elevation of Firmicutes to Bacteroidetes phyla in obese mice.