Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative splicing is a developmental switch for hTERT expression

High telomerase activity is restricted to the blastocyst stage of embryonic development when telomere length is reset, and is characteristic of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, the pathways involved in telomerase regulation as a function of pluripotency remain unknown. To explore hTERT transcriptional control, we compare genome-wide interactions (4C-seq) and chromatin accessibility (ATAC-seq) between human ESCs and epithelial cells and identify several putative hTERT cis-regulatory elements. CRISPR/Cas9-mediated deletion of candidate elements in ESCs reduces the levels of hTERT mRNA but does not abolish telomerase expression, thus implicating post-transcriptional processes in telomerase regulation. In agreement with this hypothesis, we find an hTERT splice variant lacking exon-2 and prone to degradation, to be enriched in differentiated cells but absent from ESCs. In addition, we show that forced retention of exon-2 prevents telomerase silencing during differentiation. Lastly, we highlight a role for the splicing co-factor SON in hTERT exon-2 inclusion and identify a SON mutation in a Dyskeratosis congenita patient with short telomeres and decreased telomerase activity. Altogether, our data uncover a novel alternative splice switch that is critical for telomerase activity during development.
Bisaspochalasins D and E: Two Heterocycle-Fused Cytochalasan Homodimers from an Endophytic Aspergillus flavipes.

Two heterocycle-fused cytochalasan homodimers, bisaspochalasins D (1) and E (2), were isolated from an endophytic Aspergillus flavipes. Their chemical structures were elucidated using a combination of HRESIMS, NMR, theoretical calculations, and crystallographic techniques. Bisaspochalasin D (1) is dimerized by the first reported naturally occurring triple heterobridged 3,8-dioxa-6-azabicyclo[3.2. 1]octane framework, while bisaspochalasin E (2) employs a pyrrole ring as the linking moiety. Possible dimerization mechanisms of bisaspochalasins D and E were proposed. The bioassay screening revealed that bisaspochalasin D showed cytotoxic activities against five cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) with IC50 values ranging from 4.45 to 22.99 μM. Additionally, bisaspochalasin D exhibited neurotrophic activities in a PC12 cell-based assay. At a concentration of 10 μM, bisaspochalasin D can promote neurite growth by inducing a differentiation rate of 12.52% for PC12 cells.
Salvage treatment using anti-PD-1/CTLA-4 immunotherapy after failure of neoadjuvant chemotherapy in microsatellite instable gastroesophageal carcinoma.

Perioperative chemotherapy is standard treatment for patients with early high risk gastroesophageal adenocarcinoma independent of molecular subtype. Around 8 % of gastroesophageal cancers have a microsatellite instable phenotype (MSI-H) and retrospective analyses of neoadjuvant-/adjuvant chemotherapy trials suggest no survival benefit in this patient population compared to surgery alone. Patients with advanced MSI-H malignancies obtain durable responses with immunotherapy using anti-PD-1 checkpoint blockade. We describe a case of a patient with an early MSI-H gastroesophageal adenocarcinoma who progressed on neoadjuvant chemotherapy precluding subsequent surgical resection. The patient was subsequently treated with immunotherapy using the anti-PD-1 antibody nivolumab and the anti-CTLA-4 antibody ipilimumab leading to a complete remission with biopsies of the residual tumour mass and regional lymph nodes revealing no residual tumour. This case highlights the lack of benefit from neoadjuvant chemotherapy in patients with MSI-H gastroesophageal cancers and suggests that perioperative anti-PD-1 based immunotherapy should be further investigated in this patient population. KEYPOINTS: This reports describes the successful salvage treatment of a patient with an early high risk MSI-H gastroesophageal carcinoma who progressed through neoadjuvant chemotherapy using combination immunotherapy of the anti-PD-1 antibody nivolumab and the anti-CTLA-4 antibody ipilimumab, leading to an ongoing complete remission. The case is in keeping with retrospective analyses of perioperative treatment trials demonstrating a lack of chemotherapy benefit in patients with MSI-H gastroesophageal carcinoma and supports the further investigation of anti-PD-1 based immunotherapy as treatment modality in this patient population. The case highlights the potential difficulties that may be encountered in the surgical management of patients treated with neoadjuvant immunotherapy with reactive dense fibrotic changes precluding surgical resection.
Differentiating Arteriolosclerotic Ulcers of Martorell from Other Types of Leg Ulcers Based on Vascular Histomorphology

Clinical differential diagnosis of arteriolosclerotic ulcers of Martorell is challenging due to the lack of clearly affirmative instrument-based diagnostic criteria. The aim of this study was to develop vascular histomorphological diagnostic criteria differentiating Martorell ulcers from other types of leg ulcers. The histomorphology of patients diagnosed with arteriolosclerotic ulcers of Martorell (n = 67) was compared with that of patients with venous leg ulcers, necrotizing leukocytoclastic vasculitis, pyoderma gangrenosum, and non-ulcerative controls (n = 15 each). In a multivariable logistic regression model, the rates of arteriolar calcification (odds ratio (OR) 42.71, 95% confidence interval (CI) 7.43–443.96, p < 0.001) and subendothelial hyalinosis (OR 29.28, 95% CI 4.88–278.21, p < 0.001) were significantly higher in arteriolosclerotic ulcers of Martorell. Arteriolar cellularity was significantly lower in Martorell ulcers than in controls (OR 0.003, 95 CI < 0.001–0.97, p = 0.05). However, the wall-to-lumen ratio was similar in all ulcers (OR 0.975, 95% CI 0.598–2.04, p = 0.929). Based on the Youden index, a wall cellularity of < 0.24 cells/100 μm2 was determined as the optimum cut-off point (sensitivity 0.955, specificity 0.944). Thus, arteriolar calcification, subendothelial hyalinosis, and arteriolar cellularity revealed high discriminatory power for arteriolosclerotic ulcers of Martorell.
Vulnerability to rumours during the COVID-19 pandemic in Singapore.

INTRODUCTION Amid the COVID-19 pandemic, many rumours have emerged. Given prior research linking rumour exposure to mental well-being, we conducted a nationwide survey to document the base rate of rumour exposure and factors associated with rumour vulnerability. METHODS Between March and July 2020, 1,237 participants were surveyed on 5 widely disseminated COVID-19 rumours (drinking water frequently could be preventive, eating garlic could be preventive, the outbreak arose because of bat soup consumption, the virus was created in an American lab, and the virus was created in a Chinese lab). For each rumour, participants reported whether they had heard, shared or believed each rumour. RESULTS Although most participants had been exposed to COVID-19 rumours, few shared or believed these. Sharing behaviours sometimes occurred in the absence of belief; however, education emerged as a protective factor for both sharing and belief. CONCLUSION Our results suggest that campaigns targeting skills associated with higher education (e.g. epistemology) may prove more effective than counter-rumour messages.
Policy foundations for transformation: a gender analysis of adolescent health policy documents in South Africa

Abstract The Sustainable Development Goals (SDGs) and the United Nations Global Strategy (2016–30) emphasize that all women, children and adolescents ‘survive, thrive and transform’. A key element of this global policy framework is that gender equality is a stand-alone goal as well as a cross-cutting priority. Gender inequality and intersecting social and structural determinants shape health systems, including the content of policy documents, with implications for implementation. This article applies a gender lens to policy documents by national government bodies that have mandates on adolescent health in South Africa. Data were 15 policy documents, authored between 2003 and 2018, by multiple actors. The content analysis was guided by key lines of enquiry, and policy documents were classified along the continuum of gender blind to gender transformative. Only three policy documents defined gender, and if gender was addressed, it was mostly in gender-sensitive ways, at times gender specific, but rarely gender transformative. Building on this, a critical discourse analysis identified what is problematized and what is left unproblematized by actors, identifying the key interrelated dominant and marginalized discourses, as well as the ‘silences’ embedded in policy documents. The discourse analysis revealed that dominant and marginalized discourses reflect how gender is conceptualized as fixed, categorical identities, vs as fluid social processes, with implications for how rights and risks are understood. The discourses substantiate an over-riding focus on adolescent girls, outside of the context of power relations, with minimal attention to boys in terms of their own health or through a gender lens, as well as little consideration of LGBTIQ+ adolescents beyond HIV. Dynamic and complex relationships exist between the South Africa context, actors, content and processes, in shaping both how gender is problematized and how ‘solutions’ are represented in these policies. How gender is conceptualized matters, both for policy analysis and for praxis, and policy documents can be part of foundations for transforming gender and intersecting power relations.
pH-responsive molecularly imprinted polymer for sorption and rapid desorption of dibutyl phthalate

ABSTRACT The pH-responsive molecularly imprinted polymers (SR-MIPs) for the removal of dibutyl phthalate (DBP) were obtained. The polymers were synthesized using methyl methacrylate, methacrylic acid, divinylbenzene, and a template mixed at different ratios allowing to optimize the process. The so-prepared SR-MIPs were evaluated at various pH values in processes of DBP sorption. The studies covered evaluation of uptake capacity, sorption kinetics, selectivity, and elution. The imprinted samples are characterized by improved factors comparing to their non-imprinted analogues, revealing also pH-sensitivity. The highest removal of DBP (130 mg g−1) was achieved at pH = 6, while pH-driven desorption (90%) was the most efficient at pH = 8.
Constrained generative adversarial network ensembles for sharable synthetic medical images

Abstract. Purpose: Sharing medical images between institutions, or even inside the same institution, is restricted by various laws and regulations; research projects requiring large datasets may suffer as a result. These limitations might be addressed by an abundant supply of synthetic data that (1) are representative (i.e., the synthetic data could produce comparable research results as the original data) and (2) do not closely resemble the original images (i.e., patient privacy is protected). We introduce a framework that generates data with these requirements leveraging generative adversarial network (GAN) ensembles in a controlled fashion. Approach: To this end, an adaptive ensemble scaling strategy with the objective of representativeness is defined. A sampled Fréchet distance-based constraint was then created to eliminate poorly converged candidates. Finally, a mutual information-based validation metric was embedded into the framework to confirm there are visual differences between the original and the generated synthetic images. Results: The applicability of the solution is demonstrated with a case study for generating three-dimensional brain metastasis (BM) from T1-weighted contrast-enhanced MRI studies. A previously published BM detection system was reported to produce 9.12 false-positives at 90% detection sensitivity based on the original data. By using the synthetic data generated with the proposed framework, the system produced 9.53 false-positives at the same sensitivity level. Conclusions: Achieving comparable algorithm performance relying solely on synthetic data unveils a significant potential to eliminate/reduce patient privacy concerns when sharing data in medical imaging.
Gender Differences in Theory of Mind, Empathic Understanding, and Moral Reasoning in an Offending and a Matched Non-Offending Population

Previous research suggests that a lack of pro-social skills is characteristic of an offending personality. Two hundred male and female offenders and matched controls completed measures to assess: Theory of Mind, empathic understanding, and moral reasoning. Significant differences between the offenders and the control group, as well as between the male and female participants, were detected in theory of mind, empathic understanding and moral reasoning with offenders scoring lower than the control group, and with males scoring lower than females on most tests. The ability to assess Theory of Mind, empathic understanding, and moral reasoning, and subsequently to identify reduced ability, is not only useful for researchers but will also allow practitioners to tailor existing (or develop new) interventions specific to the needs of individuals. This could be particularly useful in terms of recidivism when applied to those involved in anti-social or offending behavior.
Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19

Introduction A novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission. Methods and analysis We hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine. Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4–7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested. The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data. Ethics and dissemination The study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals. Trial registration number National Clinical Trial Registry (NCT04464408).
Risk factors and impact of early anastomotic biliary complications after liver transplantation: UK registry analysis

Abstract Background Biliary leaks and anastomotic strictures are common early anastomotic biliary complications (EABCs) following liver transplantation. However, there are no large multicentre studies investigating their clinical impact or risk factors. This study aimed to define the incidence, risk factors and impact of EABC. Methods The NHS registry on adult liver transplantation between 2006 and 2017 was reviewed retrospectively. Adjusted regression models were used to assess predictors of EABC, and their impact on outcomes. Results Analyses included 8304 liver transplant recipients. Patients with EABC (9·6 per cent) had prolonged hospitalization (23 versus 15 days; P < 0·001) and increased chance for readmission within the first year (56 versus 32 per cent; P < 0·001). Patients with EABC had decreased estimated 5-year graft survival of 75·1 versus 84·5 per cent in those without EABC, and decreased 5-year patient survival of 76·9 versus 83·3 per cent; both P < 0.001. Adjusted Cox regression revealed that EABCs have a significant and independent impact on graft survival (leak hazard ratio (HR) 1·344, P = 0·015; stricture HR 1·513, P = 0·002; leak plus stricture HR 1·526, P = 0·036) and patient survival (leak HR 1·215, P = 0·136, stricture HR 1·526, P = 0·001; leak plus stricture HR 1·509; P = 0·043). On adjusted logistic regression, risk factors for EABC included donation after circulatory death grafts, graft aberrant arterial anatomy, biliary anastomosis type, vascular anastomosis time and recipient model of end-stage liver disease. Conclusion EABCs prolong hospital stay, increase readmission rates and are independent risk factors for graft loss and increased mortality. This study has identified factors that increase the likelihood of EABC occurrence; research into interventions to prevent EABCs in these at-risk groups is vital to improve liver transplantation outcomes.
Minute ventilation/carbon dioxide production in patients with dysfunctional breathing

Dysfunctional breathing refers to a multi-dimensional condition that is characterised by pathological changes in an individual's breathing. These changes lead to a feeling of breathlessness and include alterations in the biomechanical, psychological and physiological aspects of breathing. This makes dysfunctional breathing a hard condition to diagnose, given the diversity of aspects that contribute to the feeling of breathlessness. The disorder can debilitate individuals without any health problems, but may also be present in those with underlying cardiopulmonary co-morbidities. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. This review will explore how this single measurement can be used to aid the diagnosis of dysfunctional breathing. A background discussion about dysfunctional breathing will allow readers to comprehend its multidimensional aspects. This will then allow readers to understand how VeqCO2 can be used in the wider diagnosis of dysfunctional breathing. Whilst VeqCO2 cannot be used as a singular parameter in the diagnosis of dysfunctional breathing, this review supports its use within a broader algorithm to detect physiological abnormalities in patients with dysfunctional breathing. This will allow for more individuals to be accurately diagnosed and appropriately managed. Ventilatory equivalent for CO2 can provide information to aid the diagnosis of dysfunctional breathing, particularly hyperventilation syndrome https://bit.ly/2OwTMqY
Baseline Concussion Testing Increases Agreement With Favorable Concussion Safety Decisions in Hypothetical Scenarios

Background Dangers of sports-related concussion are well documented, and those participating in sports involving significant contact are at an even higher risk relative to the general population. Despite extensive concussion education, athletes still make decisions that would be considered unsafe, such as underreporting and continuing to play despite experiencing symptoms. Although baseline testing is an increasingly common practice at all levels of sport, little is known about its ability to improve player safety perceptions. Aims The current study examines whether taking part in a standardized baseline concussion assessment changes athletes’ knowledge, attitudes, or perceptions of concussion safety decisions. Method A total of 229 club and National Collegiate Athletic Association athletes completed a modified Rosenbaum Concussion Knowledge and Attitudes Survey–Student Version (RoCKAS-ST), which was used to evaluate knowledge, attitudes, and perceptions of concussion safety decisions in hypothetical scenarios. Athletes were randomly assigned to either complete baseline concussion testing prior to the RoCKAS-ST or complete baseline testing after the RoCKAS-ST. Results Athletes randomly assigned to complete baseline testing before the RoCKAS-ST demonstrated greater agreement with favorable concussion safety decisions in hypothetical scenarios relative to athletes completing baseline testing after the RoCKAS-ST. The two conditions did not differ with respect to concussion knowledge or attitudes. Discussion Baseline testing appears to have an added benefit of resulting in more favorable perceptions toward making safe decisions following suspected concussions. Conclusion Baseline testing may provide an effective means of improving a broader constellation of concussion safety behavior, particularly in club athletes, who are typically underserved in terms of concussion-related resources and care.
Beliefs and Social Norms as Precursors of Environmental Support: The Joint Influence of Collectivism and Socioeconomic Status

The present research investigates how the cultural value of collectivism interacts with socioeconomic status (SES) to influence the basis of action. Using a U.S. national sample (N = 2,538), the research examines how these sociocultural factors jointly moderate the strength of two precursors of environmental support: beliefs about climate change and perceived descriptive norms. SES and collectivism interacted with climate change beliefs such that beliefs predicted environmental support (i.e., proenvironmental behaviors and policy support) more strongly for those who were high in SES and low in collectivism than for all other groups. This interaction was explained, in part, by sense of control. For descriptive norms, SES and collectivism did not interact but rather norms predicted action most strongly for those high in collectivism and high in SES. These findings demonstrate the theoretical and applied importance of examining multiple sociocultural characteristics together to understand the factors that drive action.
Tunable Wettability of Ferroelectric Lithium Niobate Surfaces : The Role of Engineered Microstructure and Tailored Metallic Nanostructures

An important aspect of optimizing micro- and optofluidic devices for lab-on-a-chip systems is the ability to engineer materials properties including surface structure and charge to control wettability. Biocompatible ferroelectric lithium niobate (LN), which is well-known for acoustic and nonlinear optical applications, has recently found potential micro- and optofluidic applications. However, the tunable wettability of such substrates has yet to be explored in detail. Here, we show that the contact angle of LN substrates can be reproducibly tailored between ∼7° and ∼121° by controlling the surface topography and chemistry at the nano- and micrometer scale via ferroelectric domain and polarization engineering and polarization-directed photoassisted deposition of metallic nanostructures.