bluuebunny/crossref_metadata_2025 huggingface dataset:
Freedom of Religion, Minorities, and The Law
Authors: Knights Samantha
Published: October 2023

Over the past fifty years, England has experienced considerable immigration, and as a result, the population has become increasingly religiously and culturally diverse. This plurality has inevitably raised fundamental questions about the individual and group rights and equality and non-discrimination on the one hand, with tolerance and social cohesion on the other. At a practical level the debates range from the issue of wearing religious clothing in schools to demands for the establishment of additional faith schools, through to requests for employment leave to perform religious rites. Underpinning the debate is the issue of how the political and legal system should view diversity, and how it should balance the competing interests of the individual or group against those of state or wider society, employer or educational establishment. The demands of religious groups and individuals have for some time been articulated in the public sphere and in the courts. However, the introduction of greater protection for religious minorities in English Law, including the Human Rights Act 1998, the EC Equality Directives, and the Equality Act 2006 have provided important milestones in this area. This book briefly covers the historical background to issues of religious freedom in England, and analyses the position of religion in the constitution and with regard to the legal framework including the state’s obligations under the European Convention on Human Rights. It then deals in more detail with specific areas of legal practice including education, employment, immigration, and public law, examining key case law and analysing current problems. The book combines detailed analysis with a clear assessment of the practical and procedural issues which practitioners face.
The Human Development Model of Democracy: East Asia in Perspective
Authors: Welzel Christian , Inglehart Ronald
Published: October 2023

This chapter describes theory and evidence of a model that considers the emergence, existence, and flourishing of democracies as the institutional reflection of a broader process of human development. At various points, we highlight the applicability of this model to societies in East Asia. Amartya Sen (1999) introduced the term human development. Its basic idea—the enhancement of human agency—was revised by Welzel (2002) in an attempt to give it a more explicit focus on human values and democracy.
Political Trust, Political Performance, and Support for Democracy
Authors: Wang Zhengxu , Russell J. Dalton , Shin Doh Chull
Published: October 2023

While most of our analyses reported in this volume focus on broad value orientations related to democratization and marketization in East Asia, the sentiments are also linked to citizen orientations toward the current political regime and its performance. Political culture theory argues that a regime’s perceived legitimacy is a key factor in promoting political stability, and presumably adherence to the norms of the regime (Almond and Verba 1963; Diamond 1999; Gilley 2006). In new democracies, a high level of political trust facilitates the consolidation process, while a lack of trust may contribute to political instability or a return to authoritarianism. In an authoritarian regime, an accurate measurement of the public’s trust in government provides an indication of how strongly the regime is holding its grip among the public.
The Law of Extradition and Mutual Assistance
Authors: Nicholls Clive , Montgomery Clare , Knowles Julian B
Published: October 2023

The Law of Extradition and Mutual Assistance provides a comprehensive and authoritative treatment of the laws covering the extradition arrangements between the UK and other states, as well as international mutual assistance. Since the first edition was published by Cameron May in 2002, the Extradition Act 1989 and the Criminal Justice (International Co-operation) Act 1990 have been repealed and replaced by the Extradition Act 2003 and the Crime (International Co-operation) Act 2003, respectively, and international confiscation is now dealt with under the Proceeds of Crime Act 2002. This second edition has therefore been scrupulously updated and rewritten to take into account all of the legislative changes, and offers a detailed treatment and practical guidance to the new legislation. The new edition has also been expanded to provide comparative coverage on extradition law and practice in other jurisdictions, including the US, Canada, and Australia, and includes a chapter on how the European Arrest Warrant is dealt with in other EU countries. The authors provide an expert commentary and critique of the new legislation and case law, and the book contains all relevant legislation.
‘Intelligence’ and the Division of Linguistic Labour
Authors: Sohi Kalbir , Harfield Clive
Published: October 2023

Within law enforcement the phrase ‘intelligence-led’ enjoys much currency and there has been a great deal of practitioner and academic discourse about aspects of intelligence-led policing which has included recent publication of intelligence doctrine (see, for instance, Harfield and Harfield, 2008, Chapters 2, 3 and 5). But what has emerged from the discourse and doctrine is evidence to indicate that whilst ‘intelligence’ enjoys a common currency, it may not enjoy a common meaning. This has implications particularly at a strategic and policy level. At a time when intelligence product and its role in informing decision-making has come under particular scrutiny (Bichard, 2004; Butler, 2004; Hutton, 2004; HMI Probation, 2006) this chapter explores, from the perspective of the philosophy of language, the meaning and mis-understanding of ‘intelligence’ and considers the possible implications in the arena of policing organized crime.
Developing Countries And Economies In Transition
Authors: Hoekman Bernard M , Kostecki Michel M
Published: October 2023

For a long time, the GATT was a club that was primarily of relevance to OECD countries. Developing countries did not participate fully in the exchange of concessions in negotiations, although they benefitted from generally applicable national treatment and MFN disciplines. With the creation of the WTO this changed. Developing countries became subject to a large number of obligations—some newly negotiated in the Uruguay Round, others originally negotiated during earlier rounds among industrialized nations. The resulting implementation ‘overhang’ had significant repercussions for the organization, resulting in ‘development concerns’ becoming a more prominent agenda item and the creation of mechanisms to provide assistance to developing country members. The implementation problems are part of the broader challenge of integrating developing and transition economies into the global trading system. Almost all countries have become much more open to trade and FDI, but a large subset have not sustained high growth or diversified their economies.
Safeguards And Exceptions
Authors: Hoekman Bernard M , Kostecki Michel M
Published: October 2023

Virtually all international trade agreements or arrangements contain safeguard provisions and exceptions. Broadly defined, the term ‘safeguard protection’ refers to a provision permitting governments under specified circumstances to withdraw—or cease to apply—their normal obligations in order to protect (safeguard) certain overriding interests. Safeguard provisions are critical to the existence and operation of trade-liberalizing agreements, as they function as both insurance mechanisms and safety valves. They provide governments with the means to go back on specific liberalization commitments—subject to certain conditions—should the need for this arise (safety valve). Without them, governments may refrain from signing an agreement that reduces protection substantially (insurance motive). This chapter focuses primarily on the safeguards and exceptions embodied in the GATT. Those of the GATS are either very similar or still in an embryonic stage. Safeguard provisions in the agreement on TRIPS are discussed in Chapter 8.
Plurilateral Agreements
Authors: Hoekman Bernard M , Kostecki Michel M
Published: October 2023

The GATT 1947, a treaty between contracting parties that functioned on the basis of consensus, was very difficult to amend and expand. As discussed in Chapters 1 and 2, in an effort to circumvent this problem, in the 1960s and 1970s groups of like-minded countries that sought to agree on more specific rules for policies covered by the GATT negotiated so-called codes of conduct. These codes bound only signatories, and were mostly applied on a MFN basis. Most of the existing codes were mapped into the WTO during the Uruguay Round, and their disciplines became binding upon all WTO members. They are discussed in Chapters 5 and 9. However, four Tokyo Round codes were not converted into multilateral agreements. Instead they became so-called plurilateral agreements. These bind only signatories and do not have to be applied on a MFN basis. As the WTO has no general MFN obligation—nondiscrimination requirements are contained in each of the various multilateral trade agreements—the plurilateral agreements contained in Annex 4 of the WTO are examples of what has been termed conditional MFN agreements.
Perspectives on increasing the impact and reach of CBT-I
Authors: Manber Rachel , Simpson Norah , Gumport Nicole B
Published: October 2023

Cognitive behavioral therapy for insomnia is now recognized as the front-line treatment for chronic insomnia, yet many challenges remain in improving its impact and reach. This manuscript describes our perspective on some of these challenges. Based on the literature that maladaptive cognitions predict low adherence and that high levels of cognitive-emotional hyperarousal may be associated with poor outcomes, we propose added focus on cognitive therapy strategies in CBT-I. Specifically, we propose broadening the range of traditional cognitive therapy strategies, utilizing acceptance-based strategies, and fuller integration of the broadened range of cognitive strategies into CBT-I throughout the course of treatment. We also highlight a few other promising emerging approaches to enhance the impact of CBT-I. These include involving partners to promote adherence with CBT-I treatment recommendations, using culturally relevant treatment adaptations to increase retention of patients in treatment, and using strategies for timely identification of barriers to engagement. We propose broadening the public health impact of CBT-I by integrating support for reduction in long-term use of hypnotic sleep medications, which is in line with current medical guidelines. We advocate for a case conceptualization-based approach for implementing CBT-I in a patient-centered manner, flexibly, yet with fidelity, to enhance its impact by addressing the factors above. For increasing the reach of CBT-I, we discuss the need to train more clinicians and ways to combine therapist and digital deliveries of CBT-I, highlighting stepped care strategies.
Formaldehyde induced the cardiac damage by regulating the NO/cGMP signaling pathway and L-Ca2+ channels
Authors: Bai Caixia , Zhang Fu , Yang Zhenhua , Zhang Yuexia , Guo Donggang , Zhang Quanxi
Published: October 2023

Background

Formaldehyde (FA) is a common environmental pollutant that has been found to cause negative cardiovascular effects, however, the toxicological mechanism is not well understood. In this study, we investigated the molecular effects of the Nitric Oxide (NO)/cyclic Guanosine Monophosphate (cGMP) signaling pathway and L-type calcium (L-Ca2+) channels in rat hearts.

Methods

We designed the short-term FA exposure on the rat heart in different concentrations (0, 0.5, 3, 18 mg/m3). After 7 days of exposure, the rats were sacrificed and the rat tissues were removed for various experiments.

Results

Our experimental data showed that FA resulted in the upregulation NO and cGMP, especially at 18 mg/m3. Further, when exposed to high concentrations of FA, Cav1.2 and Cav1.3 expression decreased. We conclude that the NO/cGMP signaling pathway and downstream related channels can be regulated by increasing the production of NO in the low concentration group of FA. High concentration FA directly regulates L-Ca22+ channels.

Conclusion

This study suggests that FA damages the function of the cardiovascular system by regulating the NO/cGMP signaling pathway and L-Ca2+ channels.
Cost-effectiveness of One Health interventions for rabies elimination: a systematic review
Authors: Nujum Zinia T , Asaria Miqdad , Kurup Karishma Krishna , Mini Malathi , Mazumdar Sumit , Daptardar Monal , Tiwari Harish
Published: October 2023

The ‘One Health’ (OH) approach is the most promising idea in realising the global goal of eliminating canine-mediated human rabies by 2030. However, taking an OH approach to rabies elimination can mean many different things to different people. We conducted a systematic review scrutinizing economic evaluations (EEs) retrieved from MEDLINE OVID, Embase OVID, Global Health OVID, CINAHL EBSCO and ECONLIT EBSCO that used the OH approach with the intent of identifying cost-effective sets of interventions that can be combined to implement an optimal OH-based rabies elimination program and highlight key gaps in the knowledge base. Our review suggests that an optimal OH program to tackle rabies should incorporate mass dog vaccination and integrated bite case management in combination with efficient use of post-exposure prophylaxis along with a shift to a 1-week abbreviated intradermal rabies vaccine regimen in humans. We recommend that future EEs of OH interventions for rabies elimination should be performed alongside implementation research to ensure proposed interventions are feasible and adopt a wider societal perspective taking into account costs and outcomes across both the human health and animal welfare sectors. The systematic review has been registered with PROSPERO.
T lymphocytes-related cell network in the pathogenesis of juvenile idiopathic arthritis: a key point for personalized treatment
Authors: Mazzoni Alessio , Annunziato Francesco , Maggi Laura
Published: October 2023

Purpose of review

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis of unknown origin occurring in children under 16 years of age and persisting for at least 6 weeks. Given that JIA is an inflammatory disorder, treatment strategies, including also biologicals, are focused on suppressing excessive inflammation. The finding that different patients display different responses to biological drugs supports the concept that different pathogenic mechanisms can exist in JIA, with specific cellular and molecular mechanisms driving inflammation in each patient. The aim of this review is to highlight the most recent advances in understanding the role of immune cells in JIA pathogenesis.

Recent findings

This review encompasses the role of the different cell subsets involved in sustaining inflammation in JIA, with a particular emphasis on T cells, as they orchestrate both innate and adaptive auto-reactive immunity in affected joints.

The characterization of the cellular and molecular pathways supporting inflammation will be crucial to design novel therapeutic approaches in the context of personalized medicine.
Refracture Following Operative Treatment of Pediatric Both Bone Forearm Fractures
Authors: Syed Akbar Nawaz , Ashebo Leta , Lawrence J. Todd R.
Published: October 2023

Introduction:

Both bone forearm fractures are common injuries in children. Most can be treated with reduction and casting. Those that fail nonoperative management can be treated with a plate or intramedullary fixation; however, refracture remains a problem. The goal of this study is to evaluate the refracture rate in both bone forearm fractures based on the mode of fixation.

Methods:

Institutional board review approval was obtained. A retrospective chart review from 2010 to 2021 at a single tertiary care institution was conducted for all operative patients <18 years who sustained a both bone forearm fracture. Groups were stratified based on initial operative fixation type: both bones fixated using nails, 1 bone fixated with a nail; both bones plated, and 1 bone plated. Further review was conducted to identify refractures following initial operative treatment. Statistical analyses were conducted using the χ2 test of independence and Fisher’s exact test.

Results:

In all, 402 operatively treated both bone forearm fracture patients were identified. Two hundred fifty-six of these patients underwent intramedullary fixation (average age 10.3y/o), while 146 patients received plate fixation (average age 13.8y/o). Fracture location was similar across the nailing and plating cohorts, most often occurring in the mid-shaft region. Patients aged ≤10 years refractured at a significantly higher rate than patients aged >10 years across all operative fixation cohorts (12.5% vs. 2.5%, P<0.001). Among the 256 patients who underwent intramedullary fixation, 61.3% had both bones treated (n=157/256), whereas 38.7% received single bone fixation (n=99/256). Of the 146 plate fixations, 84.4% had both bones fixed (n=123/146), and only 15.8% were treated with single bone fixation (n=23/146). In the intramedullary group, 15 patients sustained refractures, 11 of whom were treated with single bone fixation (11.1%, n=11/99) versus 4 with both both fixation (2.5%, n=4/157). Among the plating group, 7 patients sustained refractures, 6 with both bone fixation (4.9%, n=6/123) and 1 in single bone fixation (4.3%, n=1/23). Refractures were found to be significantly more prevalent among patients treated with single bone compared with both bone intramedullary nail fixation (11.1% vs. 2.5%, P=0.006). By fixated bone, single bone ulna fixations had a higher refracture rate compared with both bone fixations (12.1% vs. 3.6%, P=0.003).

Conclusion:

The overall refracture rate following operative treatment of both bone fractures is 5.5% and is similar between intramedullary and plate fixations. Overall, patients ≤10 years of age had a higher rate of refracture. Among single bone fixations, higher refracture was seen with intramedullary fixations, and when the radius was treated nonoperatively. Surgeons may be able to reduce the refracture rate by performing intramedullary fixation of both bones instead of only one bone. Effective postoperative counseling among younger patients may also decrease refracture rates.
Distributed leadership in health quality improvement collaboratives
Authors: Carstensen Kathrine , Kjeldsen Anne Mette , Nielsen Camilla Palmhøj
Published: October 2023

Background and Purpose

Distributed leadership has been suggested for describing patterns of influence in collaborative settings where public services are performed across professions and organizations. This study explores how leadership in health quality improvement collaboratives (QICs) is characterized by aligned distributed leadership practices, and how these practices relate with experienced progress and achievements in the quality improvement (QI) work.

Methods

The analysis relied on a qualitative, multicase study of two nationwide Danish QICs. Data consisted of 12 single-person and 21 group interviews with local QI teams and local and regional QIC coordinators (85 informants in total), participant observations of 34 meetings within the QICs, and a collection of documentary material. The collected data were analyzed thematically with NVivo.

Results

Leadership practices in local QI teams are characterized by aligned distributed leadership, with leadership activities being widely distributed based on negotiated, emergent practices regarding the aims, roles, and scope of the QI work. However, local quality coordinators play a pivotal role in driving the QI activities, and hierarchical support from hospital/municipal management is a precondition for the contribution of aligned distributed leadership to experienced progress and QIs.

Practice Implications

Emergent distributed leadership should be balanced by thorough consolidation of the practices to provide the best circumstances for robust QI. The active participation of formal managers and local coordinators plays a pivotal role in this consolidation and is decisive for the increased potential for long-term success and sustainability of the QI work, particularly within complex QICs.
COVID-19 Patients Presenting With Pneumothorax and Bronchopleural Fistula
Authors: Yarmohammadi Hossein , Motevalizadeh Seyyed-Alireza , Asgari Amir-Mohammad , Keshavarzi Mohammad , Azimi Ghasem
Published: October 2023

Background

COVID-19 has a variety of presentations and complications, and this study aimed to report the incidence of COVID-19 patients presenting with pneumothorax and bronchopleural fistula (BPF).

Methods

Documents of hospitalized COVID-19 patients with positive SARS-COV-2 polymerase chain reaction tests were reviewed respectively, and patients presenting with pneumothorax were included. Laboratory data, treatment, and the outcome were also gathered for each patient.

Results

The incidence of COVID-19 patients presenting with pneumothorax and BPF was 0.93% and 0.62%, respectively. Three cases were determined, and all were male adults. Two had BPF and one received thoracotomy. These 2 patients had significantly elevated inflammatory markers. Patients were treated with antibiotics, corticosteroids, anticoagulants, remdesivir, and tocilizumab. Unfortunately, all expired as 2 patients had a cardiac arrest and one had a multiorgan failure.

Conclusions

Presenting with pneumothorax among COVID-19 patients is not common but needs appropriate management to prevent further complications. It seems that BPF, as a rarely reported complication of COVID-19, might be linked to the inflammatory storm and indicates poor prognosis.
Effects of Polycyclic Aromatic Hydrocarbon Exposure and Telomere Length and their Interaction on Blood Lipids in Coal Miners
Authors: Wang Fang , Chang Li , Zhang Xingye , Jia Teng , Wang Yu , Wang Yuying , Liu Gaisheng
Published: October 2023

Objective

This study aimed to investigate the effects of polycyclic aromatic hydrocarbon (PAH) exposure and telomere length on lipids in coal miners.

Methods

Basic personal information of 637 coal miners was collected by questionnaire survey. Logistic regression, the Bayesian kernel machine regression model, and weighted quantile sum regression were used to analyze the effects of PAH metabolites and telomere length and their interactions on blood lipids.

Results

High exposure to 9-hydroxyphenanthrene (OR = 1.586, 95% CI: 1.011–2.487) and telomere shortening (OR = 1.413, 95% CI: 1.005–1.985) were associated with dyslipidemia. Weighted quantile sum results showed that 9-hydroxyphenanthrene accounted for the largest proportion of dyslipidemia (weight = 0.66). The interaction results showed that high 9-hydroxyphenanthrene exposure and short telomeres were risk factors for dyslipidemia in coal miners (OR = 2.085, 95% CI: 1.121–3.879).Conclusions:Our findings suggest that 9-hydroxyphenanthrene and shorter telomeres are risk factors for dyslipidemia, and their interaction increases the risk of dyslipidemia.
Implementing a clinical checklist for pregnant patients with opioid use disorder
Authors: Wendt Jamie Osgood , Stevenson Eleanor L. , Gedzyk-Nieman Stephanie , Koch Amie
Published: October 2023

Background:

Opioid use disorder (OUD) has been increasing in pregnant patients over the past two decades. Best practice guidelines that are available for these patients, must now be implemented by health care teams. Clinical checklists have been used for other complex patient cohorts with good success and are a potentially viable tool for ensuring best practices with this patient population as well.

Local problem:

Maine has seen a dramatic increase in the number of pregnant patients with OUD. Many of these patients seemed to “fall through the cracks” in the traditional prenatal care model. The obstetrical care team expressed feeling overwhelmed by the complex care needs of these patients and unsure of how to improve their care.

Methods:

To improve prenatal care delivery for patients with OUD, we implemented an evidence-based clinical checklist. This local, NP-led quality improvement project was done in partnership with a state-led initiative to improve perinatal care for patients with OUD.

Interventions:

An evidence-based checklist provided by the state initiative was implemented for prenatal patients with diagnosed OUD.

Results:

Use of a clinical checklist for patients with OUD increased the rate of several best practices during their prenatal care, including emergency naloxone prescription, tracking prescription monitoring reports, and contraceptive planning. Rates of completed prenatal screening for substance misuse, social determinants of health, and intimate partner violence also increased in our practice overall, as a result of this project.

Conclusions:

To further improve perinatal care coordination for patients with OUD, we recommend future evaluation of clinical checklists within various practice settings.
THE DIAGNOSIS AND TREATMENT OF LOW BACK PAIN: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline
Authors: Macedo Franz , Annaswamy Thiru , Coller Rachael , Buelt Andrew , Glotfelter Michael A. , Heideman Paul W. , Kang Daniel , Konitzer Lisa , Okamoto Casey , Olson Juli , Pangarkar Sanjog , Sall James , Spacek Lance C. , Steil Evan , Vogsland Rebecca , Sandbrink Friedhelm
Published: October 2023

Low back pain (LBP) is a significant issue in the VA and DoD populations, and the general U.S. population at large. According to the Centers for Disease Control and Prevention, 25% of U.S. adults reported having low back pain in the prior 3 months.1A survey of U.S Veterans published in 2017 revealed 33% of Veterans reported having significant back pain within the last three months.2Within the DoD, LBP was the primary diagnosis for more than 1 million medical encounters in 2020 affecting 213,331 service members.3In 2022, leadership within the U.S. Department of Veterans Affairs and U.S. Department of Defense approved a joint clinical practice guideline for the management of low back pain. Development of the guideline included a systematic evidence review which was guided by 12 key questions. A multidisciplinary team, that included clinical stakeholders, reviewed the evidence that was retrieved and developed 39 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The scope of the CPG is broad; however, the authors have focused on key recommendations that are important for clinicians in the evaluation and non-operative treatment of low back pain, including pharmacologic therapies, and both non-invasive and invasive non-pharmacologic treatments.
HIV pre-exposure prophylaxis provision by U.S. health centers in 2021
Authors: Chinbunchorn Tanat , Mayer Kenneth H. , Campbell Juwan , King Dana , Krakower Douglas , Marcus Julia L. , Grasso Chris , Keuroghlian Alex S.
Published: October 2023

Objectives:

The aim of this study was to assess HIV preexposure prophylaxis (PrEP) provision in U.S. health centers.

Design:

The U.S. Ending the HIV Epidemic (EHE) initiative designated health centers as the main healthcare system through which PrEP scale-up occurs. Health centers offer primary care to over 30 million disproportionately uninsured, racially or ethnically minoritized, and low-income patients. This study is the first to assess PrEP provision across health centers, including characteristics of clinics, patient populations, and policies associated with PrEP prescribing.

Methods:

The Health Resources and Services Administration's Uniform Data System contained aggregate data on PrEP prescriptions and patient sociodemographics at health centers from January 1 through December 31, 2021, in 50 U.S. states, the District of Columbia, and eight U.S. territories. We compared patient demographics and availability of Medicaid expansion and PrEP assistance programs at health centers that prescribed vs. those that did not prescribe PrEP.

Results:

Across 1375 health centers serving 30 193 278 patients, 79 163 patients were prescribed PrEP. Health centers that prescribed any PrEP had higher proportions of sexual, gender, racial, and ethnic minority patient populations compared with health centers that prescribed no PrEP. Compared with health centers that prescribed no PrEP, a higher proportion of health centers that prescribed PrEP were located in designated high-priority jurisdictions of the EHE initiative or states with Medicaid expansion or public PrEP assistance programs.

Conclusion:

Health centers are critical for scaling up PrEP in minoritized populations disproportionately affected by HIV, facilitated through federal and state-level policies. These findings highlight service gaps and inform future interventions to optimize PrEP implementation and support EHE initiative goals.
Antimicrobial and quorum sensing inhibitory activity of epiphytic bacteria isolated from the red alga Halymenia durvillei
Authors: Padayao Mary Hannah Rose , Padayao Francis Reuben Paul , Patalinghug Jenny Marie , Raña Gem Stephen , Yee Jonie , Geraldino Paul John , Quilantang Norman
Published: October 2023

Halymenia durvillei is a red alga that is commonly utilized in the Philippines as food and as a source of high-value natural products for industrial applications. However, there are no studies regarding the microbial community associated with H. durvillei and its potential applications. This study aimed to isolate and identify the epiphytic bacteria of H. durvillei and determine their antimicrobial and quorum sensing inhibitory (QSI) effects. The thalli of H. durvillei were collected at the shores of Santa Fe, Bantayan, Cebu, Philippines. Bacterial isolates were identified using 16S rRNA, and their ethyl acetate (EtOAc) extracts were subjected to antimicrobial susceptibility tests against representative species of yeast, Gram-negative, and Gram-positive bacteria. Their QSI activity against Chromobacterium violaceum was also determined. Fourteen distinct bacterial colonies belonging to four genera, namely, Alteromonas (3), Bacillus (5), Oceanobacillus (1), and Vibrio (5) were successfully isolated and identified. All fourteen bacterial isolates exhibited antibacterial effects. EPB9, identified as B. safensis, consistently showed the strongest inhibition against Escherichia coli, Staphylococcus aureus, and S. epidermidis having minimum inhibitory concentrations (MIC) ranging from 0.0625 – 1.0 mg mL-1. In contrast, all fourteen isolates showed weak antifungal effects. Both B. safensis (EPB 9) and B. australimaris (EPB15) exhibited QSI effects at 100 mg mL-1 showing opaque zones of  3.1 ± 0.9 mm and 3.8 ± 0.4 mm, respectively. This study is the first to isolate and identify the distinct microbial epiphytic bacterial community of H. durvillei and its potential as an abundant resource for new antibacterial and QSI bioactives.
Durability of Motor Learning by Observing
Authors: Mangos Natalia , Forgaard Christopher J. , Gribble Paul L.
Published: October 2023

Information about another person’s movement kinematics obtained through visual observation activates brain regions involved in motor learning. Observation-related changes in these brain areas are associated with adaptive changes to feedforward neural control of muscle activation and behavioural improvements in limb movement control. However, little is known about the stability of these observation-related effects over time. Here we used force channel trials to probe changes in lateral force production at various time points (1 min, 10 min, 30 min, 60 min, 24 h) after participants either physically performed, or observed another individual performing upper limb reaching movements that were perturbed by novel, robot-generated forces (a velocity-dependent force-field). Observers learned to predictively generate directionally and temporally specific compensatory forces during reaching, consistent with the idea that they acquired an internal representation of the novel dynamics. Participants who physically practiced in the force-field showed adaptation that was detectable at all time points, with some decay detected after 24 h. Observation-related adaptation was less temporally stable in comparison, decaying slightly after 1 h and undetectable at 24 h. Observation induced less adaptation overall than physical practice, which could explain differences in temporal stability. Visually acquired representations of movement dynamics are retained and continue to influence behavior for at least one hour after observation.

Significance

We used force channel probes in an upper limb force-field reaching task in humans to compare the durability of learning-related changes that occured through visual observation to those after physical movement practice. Visually acquired representations of movement dynamics continued to influence behavior for at least one hour after observation. The significance of the findings is two-fold. First, they broaden our understanding of the potential role of visual observation in naturalistic motor skill acquisition. Our findings point to a (at least) 1-hour window during which visual observation of another person (e.g. a tutor or a conspecific learner) could play a role in motor learning, especially in early learning, presumably (as shown in our previous work) through activation of the neural circuitry that underlies motor skill acquisition. Second, this one-hour window represents an opportunity for observation-based interventions in neurorehabilitation (e.g. interleaving observation with physical practice) to aid in driving cortical reorganization for recovery of motor function.
Identification of Hub Genes and Functional Annotation of Glaucoma Using Bioinformatic Analysis
Authors: Aaron Pavithren , Sivanananthan Navanithan , Kaur Jaspreet , Arumainathan Jeyvisna , Swaminathan Venkataramanan
Published: October 2023

Glaucoma is a common eye condition that damages the optic nerve, leading to vision loss and potential blindness if not treated. It affects around 80 million people worldwide and is a major cause of irreversible blindness. This study aims to identify key genes and their functions in glaucoma using bioinformatic analysis. The research follows a five-step approach, including data retrieval, processing, identification of differentially expressed genes (DEGs), protein interaction analysis, functional enrichment analysis, and identification of hub genes. Three GSE datasets (GSE 4316, GSE 53985, and GSE 7144) were selected, resulting in a total of 632 upregulated and 625 downregulated genes. Analysis using the DAVID server revealed significant biological processes related to gene regulation, transcription, and cell adhesion. The protein networks for upregulated and downregulated genes consisted of 581 nodes and 1713 edges, and 575 nodes and 2428 edges, respectively. The Cytohubba plugin identified 10 significant genes for each group. The upregulated genes included PTPRC, INS, SRC, CXCR, FN1, TNF, ACTB, AKT1, ALB, and PECAM1, while the downregulated genes included VEGFA, FN1, TP53, ACTB, AKT1, CCND1, CTNNB1, MYC, CD44, and EGFR. These findings enhance our understanding of glaucoma’s molecular biology and provide valuable insights for prognosis prediction and the development of treatments and medications.
Modulating Subjective Pain Perception with Decoded MNI-space Neurofeedback
Authors: Berman Taryn , Cushing Cody , Manuel Shawn , Vachon-Presseau Étienne , Cortese Aurelio , Kawato Mitsuo , Woo Choong-Wan , Wager Tor D. , Lau Hakwan , Roy Mathieu , Taschereau-Dumouchel Vincent
Published: October 2023

Pain is a complex emotional experience that still remains challenging to manage. Previous functional magnetic resonance imaging (fMRI) studies have associated pain with distributed patterns of brain activity (i.e., brain decoders), but it is still unclear whether these observations reflect causal mechanisms. To address this question, we devised a new neurofeedback approach leveraging real-time decoding of fMRI data to test if modulating pain-related multivoxel fMRI patterns could lead to changes in subjective pain experience. We first showed that subjective pain ratings can indeed be accurately predicted using a real-time decoding approach based on the stimulus intensity independent pain signature (SIIPS) and the neurologic pain signature (NPS). Next, we trained participants in a double-blinded decoded fMRI neurofeedback experiment to up- or down-regulate the SIIPS. Our results indicate that participants can learn to down-regulate the expression of SIIPS independently from NPS expression. Importantly, the success of this neurofeedback training was associated with the perceived intensity of painful stimulation following the intervention. Taken together, these results indicate that closed-loop brain imaging can be efficiently conducted usinga priorifMRI decoders of pain, potentially opening up a new range of applications for decoded neurofeedback, both for clinical and basic science purposes.
A machine learning-based approach to identify reliable gold standards for protein complex composition prediction
Authors: Yang Pengcheng , Lee Youngwoo , Szymanski Daniel B. , Xie Jun
Published: October 2023

Co-Fractionation Mass Spectrometry (CFMS) enables the discovery of protein complexes and the systems-level analyses of multimer dynamics that facilitate responses to environmental and developmental conditions. A major challenge in the CFMS analyses, and other omics approaches in general, is to conduct validation experiments at scale and develop precise methods to evaluate the performance of the analyses. For protein complex composition predictions, CORUM is commonly used as a source of known complexes; however, the subunit pools in cell extracts are very rarely in the assumed fully assembled states. Therefore, a fundamental conflict exists between the assumed multimerization of the CORUM “gold standards” and the CFMS experimental datasets to be evaluated. In this paper, we develop a machine learning-based “small world” data analysis method. This method uses size exclusion chromatography profiles of predicted CORUM complex subunits to identify relatively rare instances of fully assembled complexes, as well as bona fide stable CORUM subcomplexes. Our method involves a two-stage machine learning approach that is designed to leverage evolutionarily conserved sequences among CORUM subunits and integrate it with size exclusion chromatography profile data from CFMS experiments. The generated gold standards are evaluated by both statistical significance and size comparison between calculated and predicted complexes. We expect these gold standards to serve as improved benchmarks to assess the overall reliability of CFMS-based protein complex composition predictions.
Distinct rich and diverse clubs regulate coarse and fine binocular disparity processing: Evidence from stereoscopic task-based fMRI
Authors: Lohia Kritika , Soans Rijul Saurabh , Saxena Rohit , Mahajan Kabir , Gandhi Tapan K.
Published: October 2023

While cortical regions involved in processing binocular disparities have been studied extensively, little is known on how the human visual system adapts to changing disparity magnitudes. Even though there is an established correlation of BOLD signal with disparity magnitudes, this correlation is not inherent and instead arises from specific causal interactions within an integrated network. Here, we investigate causal mechanisms of coarse and fine binocular disparity processing using fMRI with a clinically validated, custom anaglyph-based stimulus. Therefore, we use degree (D) and participation coefficient (PC) metrics representing rich and diverse properties of the brain network, respectively. Twenty-six healthy participants were asked to indicate hidden 3D shapes through anaglyph filters at four disparity magnitudes. Our findings reveal significant changes at different disparity magnitudes in terms of D and PC of Middle Temporal (MT), V2, V3 and Superior Parietal Lobule (SPL) across both hemispheres. Of these, MT exhibited overlapping rich and diverse club characteristics among other brain regions. Further, diverse clubs outperform rich clubs in decoding disparity magnitudes irrespective of the hemisphere, thereby reinforcing their integrative network properties. These findings imply that distinct rich and diverse clubs exist and provide functional evidence for the variability in human stereopsis.
Evaluating discordant somatic calls across mutation discovery approaches to minimize false negative drug-resistant findings
Authors: Lin Hsin-Fu , Chien Pei-Miao , Cheng Chinyi , Yuan Tzu-Hang , Wang Yu-Bin , Chen Pei-Lung , Chen Chien-Yu , Huang Jia-Hsin , Hsu Jacob Shujui
Published: October 2023

Evaluating robustness of somatic mutation detections is essential when utilizing whole exome sequencing (WES) for treatment decision-making. A comprehensive evaluation was conducted using tumor WES from the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, in which multiple library kits sequenced identical DNA materials across three labs to benchmark analytical validity. These workflows included various read aligner (BWA, Bowtie2, DRAGEN-Aligner, DRAGMAP, and HISAT2) and mutation caller (Mutect2, TNscope, DRAGEN-Caller, and DeepVariant) combinations. The results revealed that DRAGEN exhibited superior performance, achieving mean F1-scores of 0.966 and 0.791 for SNV and INDEL detection, respectively. Among open-source software, BWA Mutect2 and HISAT2 Mutect2 combinations showed the highest mean F1-scores for SNV (0.949) and IN-DEL (0.722), respectively. The analyses indicated that high-quality data can be analyzed as having worse results, and vice versa. Evaluations of COSMIC reported mutations unveiled discrepancies across enrichment kits. IDT enrichment kits showed a higher false negative rate, while Agilent WES kits tended to miss mutations inCBLandIDH1, and Roche library kits tended to miss the mutations inPIK3CB. For drug-related biomarkers, Sentieon TNscope tended to underestimate tumor mutation burden and overlook crucial drug-resistance mutations such asFLT3(c.G1879A: p.A627T) for cytarabine resistance in leukemia andMAP2K1(c.G199A:p.D67N) forBRAFinhibitors in melanoma. The findings highlight the importance of robust bioinformatic analysis in identifying tumor mutations and guiding clinical decision-making.

Highlights

Mutation callers had a significantly higher effect on overall sensitivity than aligners.

Benchmarking analyses demonstrated that high-quality sequencing reads can be analyzed as having worse results, and vice versa.

DRAGEN exhibited the best performance among other aligner-caller combinations.

The combination of BWA with Mutect2 and HISAT2 with Mutect2 yielded the highest mean F1 scores for detecting SNVs and INDELs by open-source software, respectively.

Sentieon TNscope tended to underestimate the tumor mutation burden and missed several drug-resistant mutations.
Protein Language Model Supervised Precise and Efficient Protein Backbone Design Method
Authors: Zhang Bo , Liu Kexin , Zheng Zhuoqi , Liu Yunfeiyang , Mu Junxi , Wei Ting , Chen Hai-Feng
Published: October 2023

Proteins are essential macromolecules that play crucial roles in nearly every type of biological function. Most of the protein functions are determined by their position topologies, indicating that new functional proteins might be generated by designing their tertiary structures initially. Over the past two decades, numerous energy-based and machine learning algorithms have been proposed forde novoprotein design. However, optimizing these models to achieve a balanced performance among three critical aspects, namely sample fidelity, diversity, and generation speed, remains a challenging task on account of the constrained residue connections and hydrophobic interactions. Here we used the protein language model (pLM) as supervision to develop two complementary deep learning algorithms, Generative Protein Design by Language Model-Inpainting (GPDL-Inpainting) and GPDL-Hallucination, that can sufficiently represent and generate the protein structures and sequences. We compared the models with the state-of-the-art protein design models (RFdiffusion, RF Inpainting, and RF Halluciantion) and demonstrated that our methods can generate more designable structures with more diversity and higher computation efficiency. We also explored the possibility of the combination of hallucination and inpainting which might further improve the model efficiency and diversity. The source code of GPDL is available athttps://github.com/sirius777coder/GPDL.
On the road to losing connectivity: Fecal samples provide genome-wide insights into anthropogenic impacts on two large herbivore species in central India
Authors: Tyagi Abhinav , Yadav Nidhi , Pandit Awadhesh , Ramakrishnan Uma
Published: October 2023

Humans have impacted most of the planet, and the ensuing fragmentation results in small, isolated habitat patches posing a risk of genetic diversity loss, inbreeding and genetic load. Understanding how natural and anthropogenic landscape features affect gene flow among habitat patches is critical for maintaining connectivity. Genome-wide data is required to comprehend the impacts of recent fragmentation, which can be challenging when only non-invasive samples are available. Here, we build upon advancements in conservation genomics to address connectivity of two large herbivores, gaur (Bos gaurus) and sambar (Rusa unicolor) in central India. Given their habitat associations, we expected these species to respond similarly to habitat fragmentation. We used fecal-DNA and methylation-based host-DNA enrichment with modified ddRAD protocol to generate genome-wide single nucleotide polymorphism (SNP) data for 124 Gaur and 99 Sambar individuals. Our findings reveal that gaur populations in central India are fragmented, displaying high genetic differentiation, with drift significantly affecting small populations like Umred-Karhandala Wildlife Sanctuary. Although Sambar shows low genetic structure, another small population, Bor Tiger Reserve is genetically differentiated. Our results suggest that although landcover change and roads restrict animal movement, the extent of this impact varies across the two species. We show that different species, respond differently to landscape features, even with similar habitat associations. We highlight small and isolated populations requiring urgent conservation intervention. Such multi-species approaches enhance our understanding of cross-species connectivity patterns. We suggest shifting from single-species to multi-species holistic conservation approach in rapidly developing landscapes to better manage co-occurring endangered species.
Semantic harmonization of Alzheimer’s disease datasets using AD-Mapper
Authors: Wegner Philipp , Balabin Helena , Ay Mehmet Can , Bauermeister Sarah , Killin Lewis , Gallacher John , Hofmann-Apitius Martin , Salimi Yasamin ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Japanese Alzheimer’s Disease Neuroimaging Initiative,   the Aging Brain: Vasculature, Ischemia, and Behavior Study,   the Alzheimer’s Disease Repository Without Borders Investigators,   the European Prevention of Alzheimer’s Disease (EPAD) Consortium
Published: October 2023

INTRODUCTION

Despite numerous past endeavors for the semantic harmonization of Alzheimer’s disease (AD) cohort studies, an automatic tool has yet to be developed. As cohort studies form the basis of data-driven analysis, harmonizing them is crucial for cross-cohort analysis. We aimed to accelerate this task by constructing an automatic harmonization tool.

METHODS

We created a common data model (CDM) through cross-mapping data from 20 cohorts, three CDMs, and ontology terms, which was then used to fine-tune a BioBERT model. Finally, we evaluated the model using three previously unseen cohorts and compared its performance to a string-matching baseline model.

RESULTS

Here, we present our AD-Mapper interface for automatic harmonization of AD cohort studies, which outperformed a string-matching baseline on previously unseen cohort studies. We showcase our CDM comprising 1218 unique variables.

DISCUSSION

AD-Mapper leverages semantic similarities in naming conventions across cohorts to improve mapping performance.