bluuebunny/crossref_metadata_2025 huggingface dataset:
An In Vivo CRISPR Screening Platform for Prioritizing Therapeutic Targets in AML
Authors: Lin Shan , Larrue Clément , Scheidegger Nastassja K. , Seong Bo Kyung A. , Dharia Neekesh V. , Kuljanin Miljan , Wechsler Caroline S. , Kugener Guillaume , Robichaud Amanda L. , Conway Amy Saur , Mashaka Thelma , Mouche Sarah , Adane Biniam , Ryan Jeremy A. , Mancias Joseph D. , Younger Scott T. , Piccioni Federica , Lee Lynn H. , Wunderlich Mark , Letai Anthony , Tamburini Jérôme , Stegmaier Kimberly
Published: September 2021

CRISPR–Cas9-based genetic screens have successfully identified cell type–dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed in vitro using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies in vivo, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including SLC5A3 as a metabolic vulnerability for AML addicted to exogenous myo-inositol and MARCH5 as a critical guardian to prevent apoptosis in AML. MARCH5 repression enhanced the efficacy of BCL2 inhibitors such as venetoclax, further highlighting the clinical potential of targeting MARCH5 in AML. Our study provides a valuable strategy for discovery and prioritization of new candidate AML therapeutic targets.

Significance:

There is an unmet need to improve the clinical outcome of AML. We developed an integrated in vivo screening approach to prioritize and validate AML dependencies with high translational potential. We identified SLC5A3 as a metabolic vulnerability and MARCH5 as a critical apoptosis regulator in AML, both of which represent novel therapeutic opportunities.

This article is highlighted in the In This Issue feature, p. 275
Transscleral Removal of Subretinal Strand without Vitrectomy: A Case Report
Authors: Tang Yongping , Wu Ronghan
Published: September 2021

Recurrence of inferior retinal detachment, after vitreoretinal surgery and silicone oil tamponade, along with a subretinal strand, presents a challenge for surgeons. Vitrectomy and retinotomy are the usual treatment in such cases. Here, we present a new transscleral method for addressing this problem. A 13-year-old boy with recurrent retinal detachment after silicone oil tamponade underwent scleral buckling surgery and had a transscleral subretinal strand removed without retinotomy. The retina reattached, and silicone oil was removed 3 months later. The best-corrected visual acuity was 0.4 in decimal vision at 1 year after silicone oil removal. Scleral buckling surgery combined with subretinal strand removal may be used as an alternative to retinotomy, especially for patients with an inferior retinal detachment and local subretinal strand formation.
Molidustat for Renal Anemia in Nondialysis Patients Previously Treated with Erythropoiesis-Stimulating Agents: A Randomized, Open-Label, Phase 3 Study
Authors: Yamamoto Hiroyasu , Nobori Kiyoshi , Matsuda Yoshimi , Hayashi Yasuhiro , Hayasaki Takanori , Akizawa Tadao
Published: September 2021

Introduction: Erythropoiesis-stimulating agents (ESAs) are the current standard of care for anemia due to chronic kidney disease (CKD) in patients not undergoing dialysis. Molidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated as an alternative treatment for renal anemia. Molidustat was evaluated in five phase 3 studies, the molidustat once daily improves renal anemia by inducing erythropoietin (MIYABI) program. The present study investigated the safety and efficacy of molidustat in Japanese patients with renal anemia not undergoing dialysis and previously treated with ESAs. Methods: This was a 52-week, active-controlled, randomized (1:1), open-label, parallel-group, multicenter, phase 3 study in Japanese patients with anemia due to CKD (stages 3–5). Molidustat was initiated at 25 mg or 50 mg once daily according to previous ESA dose. The ESA darbepoetin alfa (darbepoetin) was initiated at a starting dose in accordance with the previous ESA dose and injected subcutaneously once every 2 or 4 weeks. Doses were regularly titrated to maintain hemoglobin (Hb) levels in the target range of 11.0–13.0 g/dL. The primary efficacy outcome was the mean Hb level and its change from baseline during the evaluation period (weeks 30–36). The safety outcomes included evaluation of all adverse events. Results: In total, 164 patients were randomized to receive molidustat (n = 82) or darbepoetin (n = 82). Baseline characteristics were well balanced. Mean (standard deviation) Hb levels at baseline were 11.31 (0.68) g/dL for molidustat and 11.27 (0.64) g/dL for darbepoetin. The mean (95% confidence interval [CI]) for mean Hb levels during the evaluation period for molidustat (11.67 [11.48–11.85] g/dL) and darbepoetin (11.53 [11.31–11.74] g/dL) was within the target range. Based on a noninferiority margin of 1.0 g/dL, molidustat was noninferior to darbepoetin regarding the change in mean Hb level during the evaluation period from baseline, with a least squares mean (95% CI) difference (molidustat-darbepoetin) of 0.13 (−0.15, 0.40) g/dL. The proportion of patients who reported at least 1 treatment-emergent adverse event (TEAE) was 92.7% for molidustat and 96.3% for darbepoetin. TEAEs leading to death were reported in 2 patients (2.4%) in the molidustat group and none in the darbepoetin group; serious TEAEs were reported in 32.9% and 26.8% of patients, respectively. Discussion/Conclusion: Molidustat was noninferior to darbepoetin and maintained Hb levels in the prespecified target range in patients with renal anemia not undergoing dialysis and previously treated with ESA. Molidustat was well tolerated, and no new safety signal was observed.
Potential Targets for Overactive Bladder in Older Men Based on Urinary Analysis of Metabolomics
Authors: Kira Satoru , Miyamoto Tatsuya , Tsuchiya Sachiko , Nakagomi Hiroshi , Ihara Tatsuya , Sawada Norifumi , Takeda Masayuki , Mitsui Takahiko
Published: September 2021

Objective: We investigated the association between overactive bladder (OAB) and urinary metabolites in men. Methods: This prospective observational study included 42 men aged 65–80 years. The 3-day frequency volume chart (FVC), International Prostate Symptom Score (IPSS), and quality of life score were adapted to assess the micturition behavior. Participants with IPSS urgency score ≥2 were included in the OAB group, and those with IPSS urgency score <2 were included in the control group. We performed a comprehensive metabolomic analysis using urine samples. Metabolites were compared between the groups using an unpaired t test and Fisher’s exact test in a nonadjusted analysis. Multivariable logistic regression analysis was performed to investigate the association between OAB and the metabolites. Results: Overall, 23 men were included in the OAB group and 19 in the control group. There were no differences in the background factors except age between the groups. FVC analysis demonstrated that nocturnal urine volume, 24-h micturition frequency, and nocturnal micturition frequency were significantly higher, and the maximum voided volume was significantly lower in the OAB group than in the controls. Metabolomic analysis revealed 14 metabolites that were differentially expressed between the groups. Multivariate analysis indicated that an increase in the levels of 5-iso prostaglandin F2α-VI (5-iPF2a-VI) and 5-methoxyindoleacetic acid was associated with OAB. Conclusion: Abnormal urinary metabolites, including metabolites in the tryptophan (5-methoxyindoleacetic acid, 3-indoleacetonitrile, and 3-hydroxyanthranilic acid) and arachidonic acid (5-iPF2a-VI) pathways, play a role in the pathogenesis of OAB in older men.
Germline VHL Mutation Discovered in Association with EGFR-Positive Lung Cancer and Metachronous Hepatocellular Carcinoma: A Case Report
Authors: Kuhlman Justin J. , Frier Quinn J. , Sumarriva Daniel , Oberley Matthew , Bolton Danielle , Deveras Ruby A.
Published: September 2021

VHL is a tumor suppressor gene located on chromosome 3 that is classically associated with tumors of the eye and CNS, renal cell carcinoma, and pheochromocytoma. We describe what appears to be the first report of an association between a germline VHL mutation and non-small cell lung cancer and metachronous hepatocellular carcinoma (HCC). Our case involves a 63-year-old nonsmoking male who was initially diagnosed with EGFR mutation-positive metastatic nonsquamous, non-small cell lung adenocarcinoma, who subsequently developed HCC and squamous cell carcinoma of the femur despite first-line treatment with EGFR-blocking osimertinib. Caris molecular profiling unexpectedly identified a shared underlying VHL mutation in all 3 lesions. Genetic mapping through a machine learning-based tool called Genomic Prevalence Score (GPSai™) helped determine that the femur tumor was a metastatic lesion as opposed to a separate primary and that the HCC was a distinct primary malignancy. We not only highlight the association between these tumors and a VHL mutation but also emphasize the value of next-generation sequencing and a molecular disease classifier in a patient with multiple primaries, how it helps guide therapy, and its value in guiding future studies.
Implementation of Best Practice Guidelines as an Effort in Reducing Hospital Readmission following Coronary Artery Bypass Surgery
Authors: Dinic Dragana , Milojevic Milan , Paunic Natasa , Cirkovic Andja , Peric Miodrag , Bojic Milovan , Otasevic Petar
Published: September 2021

Objectives: The present study aimed to identify significant causes of readmission within 30 days following coronary artery bypass graft (CABG) surgery and compare readmission incidence related to surgical site infections (SSIs) before and after implementing international recommendations for antibiotic prophylaxis. Methods: We analyzed 2,225 CABG patients who received either guideline-directed antibiotic prophylaxis (GDAP = 568) or institutional antibiotic prophylaxis (non-GDAP = 1,657) between January 2017 and December 2019. The primary outcome was a composite of sternal wound infection (SWI) or harvest SWI. Secondary outcomes consisted of the individual components of composite end point, the incidence of in-hospital SSIs, and prolonged postoperative length of hospital stay (LOS) (>7 days). Propensity matching was used to select pairs for final comparison. Results: Before implementing GDAP, the most frequent reason for readmission were SSIs, causing 58.2% of all readmissions within 30 days. Of 429 matched pairs, 48 patients in the GDAP group and 67 patients in the non-GDAP group were readmitted to a hospital within 30 days for any cause (11.2 vs. 15.6%, p = 0.048). We found a decreased readmission incidence for reasons related to SSIs, although these differences did not reach statistical significance (7.4 vs. 10.0%, p = 0.069). Adherence to GDAP was associated with reduced in-hospital risks of SSIs and prolonged postoperative LOS (19.6 vs. 26.6%, p = 0.015). Conclusions: In this contemporary clinical practice study, the adherence to GDAP was an insufficient measure to decrease rehospitalization due to SSIs. The present findings warrant further investigation on factors that may contribute to SSIs development after hospital discharge.
CD33 mRNA Has Elevated Expression Levels in the Leukocytes of Peripheral Blood in Patients with Late-Onset Alzheimer’s Disease
Authors: Heidari Fatemeh , Ansstas George , Ajamian Farzam
Published: September 2021

Background/Aims: In despite of conflicting results among different ethnic groups, the rs3865444 of CD33 gene has previously been identified as a risk factor for late-onset Alzheimer’s disease (LOAD).This study was aimed to evaluate the association between rs3865444 SNP with LOAD occurrence, and to investigate whether CD33 mRNA expression will change in the leukocytes of peripheral blood in LOAD patients. Methods: The rs3865444 polymorphism was genotyped in 233 LOAD and 238 control subjects using the Tetra-ARMS-PCR method. CD33 mRNAs expression in leukocytes were assessed and analyzed using the real-time qPCR method. We used in silico approach to analyze potential effects imparted by rs3865444 polymorphism in LOAD pathogenesis. Results: Our results show a significant increase in CD33 mRNA expression levels in white blood cells of LOAD patients, however, the association between CD33 rs3865444 polymorphism and LOAD was found to be not significant. We also noticed that LOAD patients with the C/A genotype had higher CD33 mRNA levels in their peripheral blood than those of the control group. Conclusions: rs3865444, located upstream of the 5′CD33 coding region, might positively influence CD33 mRNAs expression in leukocytes of LOAD versus healthy people. This is likely to happen through interfering rs3865444 (C) with the functional activity of several other transcription factors given that rs3865444 is in linkage disequilibrium with other functional polymorphisms in this coding region according to an in silico study. We propose that CD33 mRNAs elevation in peripheral immune cells – as a potential biomarker in LOAD – is related to peripheral immune system impairment.
Nasopancreatic Drainage for 4 Patients during the Early Phase of Acute Pancreatitis
Authors: Hirota Morihisa , Koiwai Akinobu , Takasu Atsuko , Kawamura Keita , Kin Ryo , Endo Katsuya , Kogure Takayuki , Meguro Takayoshi , Satoh Kennichi
Published: September 2021

We encountered 4 patients with acute pancreatitis (AP) of various etiologies and coexisting acute cholangitis who underwent endoscopic biliary stenting (EBS) and nasopancreatic drainage (NPD) via endoscopic retrograde cholangiopancreatography (ERCP) during the early phase of AP. ERCP is performed to treat acute cholangitis even in the context of AP. However, in difficult cases, accidental contrast media injection or guidewire insertion into the pancreatic duct can happen during ERCP for the purpose of EBS. It is concerned that cannulation injury and increased pancreatic duct pressure can exacerbate existing AP. Because pancreatic guidewire-associated techniques were required for all of them due to difficult biliary cannulation, we performed a NPD catheter placement using the pancreatic guidewire to decompress the pancreatic duct to prevent further exacerbating AP. Surprisingly, all patients dramatically improved without systemic or local complications. NPD could be performed without any adverse events and did not worsen the course of AP. Early decompression of a pancreatic duct using NPD may rather improve AP that had already developed. Further prospective research is needed to confirm our observations.
Innovative Standards in Oncoplastic Breast Conserving Surgery: From Radical Mastectomy to Extreme Oncoplasty
Authors: Karadeniz Cakmak Guldeniz
Published: September 2021

Background: Oncoplastic breast conserving surgery (OBCS), which is the current procedure of choice for eligible BC patients, describes a philosophy that prioritizes oncologic and cosmetic outcomes. However, knowledge gaps regarding training, acceptance, and practice preclude standardization and make it difficult to design algorithmic guidelines to optimize individualized management in the era of precision medicine. Summary: The harmony between patient expectations and oncologic goals creates the state of the art of OBCS. Nevertheless, to achieve these goals, multidisciplinary approach is a must. Surgical decisions require a comprehensive evaluation including patient factors, tumor biology, genetics, technical considerations, and adjunct therapies. Moreover, the quality-of-life (QOL) issues should be considered as the highest level of priority with a shared decision making instituted on realistic discussions with the patient. Key messages: The standardization in OBCS should be initiated via defining a breast surgeon who should gain theorical and practical competence on techniques via national or international educational programs. The algorithmic patient assessment with appropriate documentation before and after surgery should be established. A simple and safe global lexicon should be designed regarding techniques to be proposed and quality metrics to be considered. Additionally, international multicenter prospective trials should be instituted to overcome knowledge gaps. It is evident that OBCS is the perfect union of science with art. Nevertheless, at the very end, the question is not the nature of the surgeon/artist who would be the extremist, the innovator, or the conservative, but the patient’s satisfaction, prognosis, and QOL that conclude the cascade of state of the art of OBCS.
Increased Expression of miR-7a-5p and miR-592 during Expansion of Rat Dental Pulp Stem Cells and Their Implication in Osteogenic Differentiation
Authors: Rong Weiqiong , Rome Calvin , Yao Shaomian
Published: September 2021

Dental pulp stem cells (DPSCs) possess strong osteogenic differentiation potential and are promising cell sources in regenerative medicine. However, such differentiation capacity progressively declines during their in vitro expansion. MicroRNAs (miRNAs) play important roles in modulating stem cell differentiation. This study aimed (1) to determine if miR-7a-5p and miR-592 are involved in maintaining and regulating osteogenic differentiation of DPSCs, and (2) to explore their potential regulatory pathways. We found that the expression of miR-7a-5p and miR-592 was significantly upregulated during the expansion of rat DPSCs (rDPSCs). Overexpression of these miRNAs inhibited the osteogenic/odontogenic differentiation of rDPSCs, as evidenced by calcium deposition and osteogenic/odontogenic gene expression. RT-qPCR determined that miR-592 could downregulate heat shock protein B8, whose expression is reduced during the expansion of rDPSCs. Furthermore, RNA-seq and bioinformatics analysis identified significant signaling pathways of miR-7a-5p and miR-592 in regulating osteogenic differentiation, including TNF, MAPK, and PI3K-Akt pathways. We conclude that upregulating miR-7a-5p and miR-592 suppresses the osteogenic differentiation of rDPSCs during their in vitro expansion, likely via TNF, MAPK, and PI3K-Akt pathways. The results may shed light on application of miR-7a-5p and miR-592 for maintaining osteo-differentiation potential in stem cells for bone regeneration and bone-related disease treatment.
Growing Racial Resilience: The Impact of Mindsets on the Development of Prejudice
Authors: Tai Christine , Pauker Kristin
Published: September 2021

Previous studies have indicated a strong link between lay theories and the development of prejudice. The purpose of this article is to review past studies that have examined the relation between a specific lay theory (mindset) and the development of prejudice, as well as highlight areas for future research that will contribute to our theoretical understanding of mindsets (and their relation to prejudice). Specifically, we highlight the need for future studies to examine mindsets from the target’s perspective, to explore how contextual cues may influence the development of mindsets over time, and to observe how mindsets motivate collective action among majority group members. Future studies focused on these areas will deepen the field’s theoretical understanding of the impact of mindsets on the development of prejudice. Such knowledge, in turn, can inform the construction of future mindset interventions that foster sustainable and concrete improvements in interracial relations and ultimately promote racial equity.
Influence of Janus Kinase Inhibitors on the Neuronal Activity as a Proof-of-Concept Model for Itch
Authors: Wohlrab Johannes , Stintzing David , Schultz Luise , Jügelt Konstantin , Schroeder Olaf H.-U.
Published: September 2021

Background: Itching is considered to be a subjective symptom of the activation of neurosensory structures by different signal molecules and trigger factors. The signaling cascades responsible for it are closely linked to inflammatory processes. This explains why itching also occurs in many inflammatory diseases. One of these signaling cascades is mediated by Janus kinases (JAKs). Recently, it could be shown on a molecular level that Janus kinase 1 (JAK1) directly activates frontal cortex neurons and thus can cause chronic itching. Objectives: This study deals with the influence of different JAK inhibitors (JAKi) on the activity of chip-based neural networks of cultured frontal cortex neurons by investigating neurophysiological activity parameters. This in vitro model provides information on dose-dependent effects of model substances with different specificity regarding the inhibition of different JAKs. Methods: Tofacitinib (pan-JAKi), baricitinib (JAK1/2i), and upadacitinib (JAK1i) in a concentration range from 10 nmol/L to 50 μmol/L were tested in a microelectrode array neurochip culture system. Results: The results show that the inhibition of the neuronal activity of frontal cortex neurons increases with JAK1 selectivity and is dependent on concentration. Conclusion: These observations are supported by data from clinical studies in atopic dermatitis and psoriasis. The clinical relevance of these results must be proven by further clinical studies with subjective and objective parameters for itching.
Identification key for anuran amphibians in a protected area in the northeastern Atlantic Forest
Authors: Dubeux Marcos Jorge Matias , Nascimento Filipe Augusto Cavalcanti do , Gonçalves Ubiratan , Mott Tamí
Published: September 2021

The identification of anuran amphibians is still a challenge in megadiverse assemblages. In the Neotropics, the Atlantic Forest harbors more than 600 anuran species, and many studies in this ecoregion report anuran assemblages surpassing 30 species. Taxonomic keys facilitate the identification of biological diversity, however only a few are available for anuran assemblages in the Atlantic Forest. Herein we present an identification key for 40 anuran species distributed across 20 genera and nine families, occurring in the Environmental Protection Area of Catolé and Fernão Velho, northeastern Atlantic Forest. Thirty-five morphological characteristics were used in the key, all of which can be easily observed in living and museum specimens. This pioneer study provides the first identification key for an amphibian assemblage in the northeastern Atlantic Forest and this baseline information acts as the starting point for the development of evolutionary and ecological research in this conservation unit.
The developmental variations of the sagitta otolith in the young and mature male of a hermaphrodite polynemidae fish, Eleutheronema tetradactylum (Shaw, 1804)
Authors: Roy Soumen , Bardhan Itika
Published: September 2021

The Eleutheronema tetradactylum is a protandrous, hermaphrodite, marine perciformes fish. The body length of this fish acts as an important diagnostic marker for male and female discrimination. The present study describes for the first time the ultrastructural characteristics on the medial surface of the sagitta otolith in different body size groups of males of E. tetradactylum (Polynemidae: Perciformes) using scanning electron microscopy. The sagitta is a spindle-shaped structure that includes a well-developed rostrum and a poorly developed antirostrum. The sulcus is ostio-pseudocaudal type, almost straight and devoid of the collum. The ostium is a well-developed, vase-shaped structure. The cauda includes the colliculum and a well-developed caudal bulb with several distinct growth stripes. The length of the caudal bulb is significantly correlated to the growth of the body size of the fish. The excisura major is indistinct and the excisura minor is absent. The cristae are distinct on both sides of the sulcus. The one-way ANOVA test revealed that the development of several sagitta features shows significant differences in various body size groups of E. tetradactylum. The growth of the sagitta length is more closely related to the fork length than the sagitta width. Therefore, the sagitta length and the caudal bulb length can be used as important predictors to evaluate the fish size. The cauda region of the sagitta in E. tetradactylum is unique as well as more decorative than those of another Polynemidae fish and other hermaphrodite, marine perciformes fishes. The sagitta characteristics of E. tetradactylum might be advantageous in the identification of the sex and the taxonomy of the hermaphrodite fish species.
Efficient Correction of a Hypertrophic Cardiomyopathy Mutation by ABEmax-NG
Authors: Ma Shuhong , Jiang Wenjian , Liu Xujie , Lu Wen-Jing , Qi Tao , Wei Jingjing , Wu Fujian , Chang Yun , Zhang Siyao , Song Yabing , Bai Rui , Wang Jianbing , Lee Andrew S. , Zhang Hongjia , Wang Yongming , Lan Feng
Published: September 2021

Rationale:

Genetic editing has shown great potential for the treatment of human hereditary disorders via the elimination of mutations in embryos. However, the efficiency and safety of germline gene editing are not well understood.

Objective:

We aimed to examine the preclinical efficacy/safety of embryonic base editing in a mouse model of hypertrophic cardiomyopathy (HCM) using a novel adenine base editor (ABE) platform.

Methods and Results:

Here, we described the use of an ABEmax-NG to directly correct the pathogenic R404Q/+ mutation (
Myh6
c.1211C>T) in embryos for a mouse model of HCM, increasing the number of wild-type embryos for in vitro fertilization. Delivery of the ABEmax-NG mRNA to embryos from R404Q/+ HCM mice resulted in 62.5% to 70.8% correction of the
Myh6
c.1211C>T, reducing the level of mutant RNA and eliminating HCM in the postnatal mice as well as their offspring. In addition, the same single guide RNA was also used to target an intronic locus (chr2: +36,585,842) with an overall editing rate of 86.7%, thus confirming that ABEmax-NG can efficiently edit target loci with different protospacer adjacent motifs (PAM) and genomic distribution in vivo. Compared with CRISPR/single-stranded oligodeoxynucleotides–mediated correction, ABEmax-NG displayed a much higher correction rate without introducing indels. DNA and RNA off-target analysis did not detect off-target editing in treated embryos and founder mice. In utero injection of adeno-associated virus 9 encoding the ABEmax-NG also resulted in around 25.3% correction of the pathogenic mutation and reduced of mutant RNA, thereby indicating ABEmax-NG has the potential to correct the HCM mutation in vivo.

Conclusions:

We developed an ABEmax-NG system, which efficiently corrected a pathogenic
Myh6
HCM mutation in mouse embryos without off-target lesions, thus safely eliminating HCM in derived mice and their progeny.
Reporting of Results by Sex in Randomized Controlled Trials of Acute Stroke Therapies (2010–2020)
Authors: Pudar Julia , Strong Brent , Howard Virginia J. , Reeves Mathew J.
Published: September 2021

Background and Purpose:

When reporting primary results from randomized controlled trials, recommendations include reporting results by sex. We reviewed the reporting of results by sex in contemporary acute stroke randomized controlled trials.

Methods:

We searched MEDLINE for articles reporting the primary results of phase 2 or 3 stroke randomized controlled trials published between 2010 and June 2020 in one of nine major clinical journals. Eligible trials were restricted to those with a therapeutic intervention initiated within one month of stroke onset. Of primary interest was the reporting of results by sex for the primary outcome. We performed bivariate analyses using Fisher exact tests to identify study-level factors associated with reporting by sex and investigated temporal trends using an exact test for trend.

Results:

Of the 115 studies identified, primary results were reported by sex in 37% (n=42). Reporting varied significantly by journal, with the
New England Journal of Medicine
(61%) and
Lancet
journals (40%) having the highest rates (
P
=0.03). Reporting also differed significantly by geographic region (21% Europe versus 48% Americas,
P
=0.03), trial phase (13% phase 2 versus 40% phase 3,
P
=0.05), and sample size (24% <250 participants versus 61% >750 participants,
P
<0.01). Although not statistically significant (
P
=0.11), there was a temporal trend in favor of greater reporting among later publications (25% 2010–2012 versus 48% 2019–2020).

Conclusions:

Although reporting of primary trial results by sex improved from 2010 to 2020, the prevalence of reporting in major journals is still low. Further efforts are required to encourage journals and authors to comply with current reporting recommendations.
Sources of Learning: Zhu Xi’s Theory of Moral Development
Authors: Song Jaeyoon
Published: September 2021

As moral philosopher Zhu Xi (1130–1200) sought to nurture the autonomous moral self. In his pedagogical scheme, one ought to cultivate the innate goodness of the heart, investigate principles in things, and embody ethical standards in daily life. In Zhu Xi’s view, the ability to exercise moral autonomy is obtained through a long period of moral and ethical training under the close surveillance of one’s immediate surroundings since early childhood. For this reason, Zhu Xi emphasized the practice of social norms as well as the performance of mundane rituals as the preconditions for the development of the autonomous moral self. By combining the Lesser Learning (xiaoxue 小學) with the Great Learning (daxue 大學), Zhu Xi articulated an integrated vision of moral development from the heteronomous performing of ethical duties to the autonomous embodiment of moral principles.
The standard deviation structure as a new approach to growth analysis in the farmed Pacific white shrimp, Penaeus vannamei (Decapoda, Penaeidae)
Authors: Castillo-Vargasmachuca Sergio G. , Aragón-Noriega E. Alberto , Ponce-Palafox Jesús T. , Rodríguez-Domínguez Guillermo , De los Santos Raúl Claro
Published: September 2021

In the present study, weight-at-age data of reared Pacific white shrimp, Penaeus vannamei Boone, 1931, were analysed under four different assumptions of variance (observed, constant, depensatory, and compensatory variance) in order to analyse the robustness for selecting the right standard deviation structure to parametrize the Von Bertalanffy, Logistic and Gompertz models. Selection of the best model and variance criteria were obtained based on the Bayesian information criterion (BIC). According to the results of the BIC, the observed variance in the present study proved to constitute the best way to parametrize the three above-listed growth models, and the Von Bertalanffy model appeared to be the best to represent the growth curve found. This is an asymptotic sigmoid curve with an inflection point. Based on these results, using the observed error structure to calculate the growth parameters in multi-model inference analyses is recommended.
Two new species of the problematic harpacticoid genus Itunella (Copepoda, Canthocamptidae)
Authors: Karanovic Tomislav
Published: September 2021

The genus Itunella Brady, 1896 has a troubled taxonomic past, partly because of paucity of its members, but mostly because of inadequate research. A lack of detail in species descriptions and redescriptions, absence of alternative methods for testing species hypotheses, combined with a notion that most marine and estuarine animals have wide distributions and enormous intraspecific variability, all resulted in blurring of some interspecific boundaries, synonymizing without examination of the type material, and founding species diagnoses on dubious characters. Itunella yeondeokensis sp. nov. is described here in great detail from a small sandy beach on the east coast of Korea. It differs from all reported and illustrated congeners by an extremely long inner apical seta on the third exopodal segment of second to fourth swimming legs. This is the second member of this genus from Korea, the first one being described from three estuaries also on the east coast. All other congeners are European species. An overview of all published species and records of this genus is provided, as well as a dichotomous key to valid species to aid in their identification. Itunella kieferi sp. nov. is a new name for a single female from Germany, previously reported as a member of a widely distributed and polymorphic species.
Admissibility of Evidence Obtained by Torture and Inhuman or Degrading Treatment. Does the European Court of Human Rights Offer a Coherent and Convincing Approach?
Authors: Jasiński Wojciech
Published: September 2021

The paper presents and assesses the approach of the ECtHR to admissibility of evidence obtained through torture and inhuman or degrading treatment in the criminal process. The author examines the content of the standard, its justifications and the consistency of the ECtHR's reasoning. The paper refers both to the admissibility of statements and real evidence as well as to primary and derivate evidence obtained in violation of Article 3 echr. The admissibility of evidence obtained by oppressive conduct of private individuals is also analysed. The assessment of the Strasbourg Court’s case law indicates that its approach is quite nuanced and, unfortunately, inconsistent and incoherent. Its main shortcoming is the lack of an in-depth analysis of the rationale for the inadmissibility of evidence obtained by maltreatment and the piecemeal treatment of individual categories of such evidence devoid of attempt to comprehensively address its admissibility in criminal proceedings.
Christians, Jews, and Muslims in the Syriac Story of the Mystery Hidden in the Eucharistic Offering
Authors: Minov Sergey
Published: September 2021

This article contains the unpublished Syriac text of the Story of the Mystery Hidden in the Eucharistic Offering, an anonymous hagiographical composition that tells the story of the conversion of a Muslim king. The text of the Story, published on the basis of two manuscripts (Birmingham, Cadbury Research Library, Mingana Syr. 71, and Manchester, John Rylands Library, Syr. 59), is accompanied by an English translation and discussion of its message.
You Are Here: Mapping Religious Studies in Canada
Authors: Bramadat Paul
Published: September 2021

This short essay introduces the contributions to this special section of Studies in Religion.
Contributions and Challenges in Health Lifestyles Research
Authors: Mollborn Stefanie , Lawrence Elizabeth M. , Saint Onge Jarron M.
Published: September 2021

The concept of health lifestyles is moving scholarship beyond individual health behaviors to integrated bundles of behaviors undergirded by group-based identities and norms. Health lifestyles research merges structure with agency, individual-level processes with group-level processes, and multifaceted behaviors with norms and identities, shedding light on why health behaviors persist or change and on the reproduction of health disparities and other social inequalities. Recent contributions have applied new methods and life course perspectives, articulating health lifestyles’s dynamic relationships to social contexts and demonstrating their implications for health and development. Culturally focused work has shown how health lifestyles function as signals for status and identity and perpetuate inequalities. We synthesize literature to articulate recent advances and challenges and demonstrate how health lifestyles research can strengthen health policies and inform scholarship on inequalities. Future work emphasizing health lifestyles’s collective nature and attending to upstream social structures will further elucidate complex social processes.
Online quality prediction based on the double cumulative model for multiphase batch processes with transitions
Authors: Tang Xiaochu , Li Yuan
Published: September 2021

In multiphase batch processes, the final product quality prediction results depend on the common cumulative effects of all the critical phases with transitions on quality rather than a separated one. However, the common cumulative effect are rarely considered at the same time. To address this issue, a double cumulative model is proposed in this paper. The double model includes the internal cumulative model and the external cumulative model. On one hand, the critical local cumulative quality is introduced to isolate the local cumulative effect of different phases and transitions in the internal cumulative model. Especially, for transitions modeling, an average process trajectories method based on the dominant phase identification is developed to deal with the dynamic and uncertainty. On the other hand, the correlation of different cumulative models is extracted by constructing the external cumulative model. In this way, the cumulative effect of all the phases and transitions are considered simultaneously. The proposed method is applied to penicillin fermentation. The simulation results demonstrate the effectiveness and superiority of the proposed method over the competing models.
Thyroid Hemiagenesis Accompanying an Ectopic Lingual Thyroid
Authors: Chuang Kai-Fen , Lee Jih-Chin , Lee Che-Jui
Published: September 2021

Lingual thyroid is an uncommon condition and cases accompanying thyroid hemiagenesis are rarely documented. Patients with thyroid hemiagenesis are usually asymptomatic and generally diagnosed incidentally. Herein, we reported the case of thyroid hemiagenesis accompanying an ectopic lingual thyroid with euthyroidism and presented with regional symptoms.
The nine development bands: A conceptual framework and global theory for waste and development
Authors: Whiteman Andrew , Webster Mike , Wilson David C
Published: September 2021

Solid waste management (SWM) is an essential utility service. More than two to three billion people worldwide still lack basic services, whereas some countries are already moving beyond SWM towards waste and resource management (WaRM) and a circular economy. This paper sets out a novel conceptual framework and global theory of waste and development, providing a road map, allowing a country or city to locate their current position and plot their way ahead. We identify nine development bands (9DBs) with significant commonalities in terms of critical challenges and developmental pressure points. DB1–DB4 reflect stepwise improvement towards the new baseline of meeting the SDG 11.6.1 indicators of universal collection and management in controlled facilities (DB5). Countries can then choose to move towards environmentally sound management and the ‘reduce, reuse, recycle’ (3Rs) (DB6-9), with an ultimate aspiration of ‘zero waste’. We test the 9DBs conceptual framework against historical journeys of higher income countries. The main application will be in low- and middle-income countries striving towards SDG 11.6.1, where it fills a key gap in the practitioners’ toolkit by enabling initial framing/scoping of the problem and smarter interventions to be designed and sense checked. Key insights include targeted governance/institutional reforms, appropriate and affordable systems/technology and adapting solutions to a diversity of local needs and realities.
Development of poly (vinylidene fluoride)/silver nanoparticle electrospun nanofibre mats for energy harvesting
Authors: Thotadara Shivalingappa Roopa , Narasimha Murthy Hebbale Narayana Rao , Purushothaman Pradeep , Badiger Prasanna , Savarn Swapnil , Majumdar Utsav , Angadi Gangadhar
Published: September 2021

Energy harvesting using piezoelectric materials finds attention of researchers due to miniaturisation. Polyvinylidene fluoride (PVDF) is one such polymeric material with high piezoelectric and pyroelectric properties and hence is used for sensors, actuators, energy harvesting and biomedical devices. This study reports electrospinning of PVDF/Ag nanoparticles (AgNP) nanofibre mats for energy harvesting. Nanofibre mats were prepared by adopting voltage (20 kV), flow rate (1.5 mL/hour) and tip to collector distance (19 cm). The fibre mats were characterised using Fourier-Transformed Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). FTIR and XRD results showed 11.84% and 36.36% increase in β-phase and crystallinity, respectively, due to the addition of 1.5 wt. % AgNP to PVDF. SEM micrographs showed decrease in bead formation and increase in fibre diameter from 40 nm to 355 nm due to the addition of AgNP. Sensitivity and voltage output were studied. The fibre mats were used for development of a miniature burglar alarm system, and its response to the applied pressure was tested.
Integrating Palliative Care Into a Neurosurgical Intensive Care Unit (NS-ICU): A Quality Improvement (QI) Project
Authors: Poi Choo Hwee , Koh Mervyn Yong Hwang , Koh Tessa Li-Yen , Wong Yu-Lin , Mei Ong Wendy Yu , Gu Chunguang , Yow Fionna Chunru , Tan Hui Ling
Published: September 2021

Objectives:

We conducted a pilot quality improvement (QI) project with the aim of improving accessibility of palliative care to critically ill neurosurgical patients.

Methods:

The QI project was conducted in the neurosurgical intensive care unit (NS-ICU). Prior to the QI project, referral rates to palliative care were low. The ICU-Palliative Care collaborative comprising of the palliative and intensive care team led the QI project from 2013 to 2015. The interventions included engaging key stake-holders, establishing formal screening and referral criteria, standardizing workflows and having combined meetings with interdisciplinary teams in ICU to discuss patients’ care plans. The Palliative care team would review patients for symptom optimization, attend joint family conferences with the ICU team and support patients and families post-ICU care. We also collected data in the post-QI period from 2016 to 2018 to review the sustainability of the interventions.

Results:

Interventions from our QI project and the ICU-Palliative Care collaborative resulted in a significant increase in the number of referrals from 9 in 2012 to 44 in 2014 and 47 the year later. The collaboration was beneficial in facilitating transfers out of ICU with more deaths outside ICU on comfort-directed care (96%) than patients not referred (75.7%, p < 0.05). Significantly more patients had a Do-Not-Resuscitation (DNR) order upon transfer out of ICU (89.7%) compared to patients not referred (74.2.%, p < 0.001), and had fewer investigations in the last 48 hours of life (p < 0.001). Per-day ICU cost was decreased for referred patients (p < 0.05).

Conclusions:

Multi-faceted QI interventions increased referral rates to palliative care. Referred patients had fewer investigations at the end-of-life and per-day ICU costs.
The unused potential of process tracing as evaluation approach: The case of cluster policy evaluation
Authors: Rothgang Michael , Lageman Bernhard
Published: September 2021

This article shows that process tracing developed in social science research can be used in evaluations of complex structural and technology policy programmes to overcome deficits in the methodological instruments used to date. Cluster policies are a well-suited example because they are characterized by complex impact patterns like many other current structural and innovation policy programmes. The origin and characteristics of the methodological approach of process tracing are discussed and weaknesses of impact evaluations of cluster programmes highlighted. Subsequently, we look at the potentials of process tracing in impact evaluations of cluster programmes within the framework of mixed-method designs. Our analysis shows that process tracing can enrich the applied methodological repertoire. It allows the evaluators to test the accuracy of the theoretical assumptions underlying the analysed programme and to identify causal mechanisms.
Messiness in international qualitative interviewing: What I did, what I didn’t do, and a little bit about why
Authors: Field Rebecca Soraya , Barns Angela , Chung Donna , Fleay Caroline
Published: September 2021

This is a reflexive account of the messiness experienced by a Persian-Australian doctoral researcher interviewing social work and human service practitioners and people seeking asylum in Germany. This data collection was part of a cross-national comparative study of the impacts of policy on the experiences and perceptions of people seeking asylum and social work and human service practitioners in Bavaria and Western Australia. Through interview stories and the work of others, this article offers a first person account of the complexities, ambiguities and dilemmas that can occur before, during and after data collection, how these were navigated through the use of Finlay's (2012) five lenses for the reflexive interviewer, and some of the lessons learnt.
D4F alleviates the C/EBP homologous protein-mediated apoptosis in glycated high-density lipoprotein-treated macrophages by facilitating autophagy
Authors: Tian Hua , Zhang Zhaoqiang , Han Xiaoyan , Pan Tianqi , Tao Geru , Jiao Peng , Zhai Lei , Yang Libo , Wang Xiaoxu , Yao Yilin , Qin Shucun , Yao Shutong
Published: September 2021

The present study aimed to investigate the role of D4F, an apolipoprotein A-I mimetic peptide, in macrophage apoptosis induced by the glycated high-density lipoprotein (gly-HDL)-induced endoplasmic reticulum (ER) stress C/EBP homologous protein (CHOP) pathway, and unravel the regulatory role of autophagy in this process. Our results revealed that except for suppressing the accumulation of lipids within RAW264.7 macrophages caused by gly-HDL, D4F inhibited gly-HDL-induced decrease in the cell viability and increase in lactate dehydrogenase leakage and cell apoptosis, which were similar to 4-phenylbutyric acid (PBA, an ER stress inhibitor). Besides, similar to PBA, D4F inhibited gly-HDL-induced ER stress response activation evaluated through the decreased PERK and eIF2α phosphorylation, together with reduced ATF6 nuclear translocation as well as the downregulation of GRP78 and CHOP. Interestingly, D4F facilitated gly-HDL-triggered activation of autophagy, measured as elevated levels of beclin-1, LC3-II, and ATG5 expressions in macrophages. Furthermore, the inhibition effect of D4F on gly-HDL-induced ER stress-CHOP-induced apoptosis of macrophages was restrained after beclin-1 siRNA and 3-methyladenine (3-MA, an inhibitor of autophagy) treatments, while this effect was further reinforced after rapamycin (Rapa, an inducer of autophagy) treatment. Furthermore, administering D4F or Rapa to T2DM mice upregulated LC3-II and attenuated CHOP expression, cell apoptosis, and atherosclerotic lesions. However, the opposite results were obtained when 3-MA was administered to these mice. These results support that D4F effectively protects macrophages against gly-HDL-induced ER stress-CHOP-mediated apoptosis by promoting autophagy.
Exploring Kurdish Islamist Civil Society and Conflict in Turkey (2015–2018)
Authors: Ozcelik Burcu
Published: September 2021

This article addresses the role and impact of religious civil society in situations of armed conflict through a case study of Kurdish Islamist civil society organisations and activists in Turkey. The focus is on the period following the collapse of the peace process and resurgence of violence in mid-2015 between Turkish security forces and the Kurdistan Workers’ Party (Partiya Karkêrên Kurdistanê). Based on 40 in-depth interviews conducted in the city of Diyarbakir, I identify three main challenges to the effectiveness of religious civil society in peacebuilding processes: (1) relations with the state, (2) legacy and relationship with institutional violence, and (3) advocacy and representation of community needs. This article shows how ethnicity and Islam are shifting, contingent interactions in the construction of Kurdish identity, especially in response to violence. Although the public expression of pro-Kurdish rights claims altered under a securitisation rubric during this period, the demand for a peaceful settlement to the conflict transcends ideological and social differences across many Kurds.