bluuebunny/crossref_metadata_2025 huggingface dataset:
Grace and Sin
Authors: Apetrei Sarah
Published: December 2023

This chapter examines the gender implications of the new wave of free-grace doctrine in the period of the Revolution, and its reception and development by women; and, conversely, the reappraisal of the doctrine of sin. The first part considers the strongly gendered imagery framing free-grace theology: not least that which accompanied a liberative narrative of the redeemed soul as the free woman in contrast to the bond woman, based on the typology of Sarah and Hagar. Highly feminized images of a maternal Christ also surfaced in the context of the spirituality of free grace, in the visionary writings of Anna Trapnel and Sarah Wight (who influenced Trapnel). The second part considers the gendered reconceptualization of sin as tyranny and oppression, a patriarchal or masculine abuse of power, especially in the writings of Gerrard Winstanley.
Song
Authors: Apetrei Sarah
Published: December 2023

This chapter considers the significance of singing as a form of prophetic utterance, and especially women’s song, in the radical theological networks of the period of the Revolution. Apocalyptic singing, whether extempore or scripted in hymn form, was practised widely in the radical congregations of the 1640s and 1650s, and signalled the renovation of worship and the advent of the new Jerusalem with its new ‘psalms’. Women were centrally and prominently involved in the prophetic act of singing the songs of Sion as a revolutionary sign. Spiritual singing was considered a manifestation of the new birth, like the Magnificat: the proclamation of the living Christ incarnate in the saints, and heaven’s condescension to earth.
Church
Authors: Apetrei Sarah
Published: December 2023

This chapter examines the gendered dimensions of the confrontation between mystical radicals and ecclesiastical institutions in the English Revolution. The chapter explores how the radicals’ disruptive understanding of Christian communion, the underlying anthropology which supported that understanding, and their abandonment of clerical hierarchy contributed to an environment hospitable to female participation. It also considers afresh the influence on anti-confessionalism in the English Revolution of two sixteenth-century radical traditions: the Family of Love, and Paracelsianism, both movements with deeply spiritualist ecclesiologies, and irenic or quietistic tendencies in other European settings. The biographies and visionary preaching of the army preachers, Henry Pinnell and William Sedgwick, and those of Elizabeth Avery are considered in this chapter. Sedgwick in particular is reinterpreted as a highly original thinker, exploring a remarkably egalitarian relationship of reciprocity between Christ and the church, with strong implications for gender relations.
Conclusion
Authors: Apetrei Sarah
Published: December 2023

The Conclusion traces both the biographical outlines of the women and radical preachers considered in the study, and their reputations in the period after the Revolution. The reputations of radical women, it is suggested, were mixed, and the chapter illustrates how certain dissenting groups and voices remembered female pioneers or reformers. Rather than arguing that the revolutionary generation left a long-term legacy to political and feminist activism, the Conclusion argues that the significance of the study lies instead not only in its contextualization of radical theology and women’s activism, but also in the illustration of the dynamic change that a different perspective, especially the marginalized perspective, brings to intellectual life.
A Pattern Theory of Self
Authors: Gallagher Shaun
Published: December 2023

This chapter develops a pluralist conception of self, outlining the notion of the self-pattern. It provides some background to the idea of a pattern theory, with a focus on a pattern theory of emotion. It then specifies in some detail a candidate list of various factors or processes involved in the self-pattern. These include bodily processes, prereflective experiential processes, affective, behavioral, intersubjective, cognitive-psychological, reflective, and narrative processes, as well as ecological and normative factors. The self-pattern is not just a collection of such processes, but a gestalt defined by dynamical relations. The chapter then explores some philosophical issues about what to include in the self-pattern, and concludes by identifying some benefits of thinking of the self and its disorders in this way.
Dynamical Relations in the Self-pattern and Psychopathology
Authors: Gallagher Shaun
Published: December 2023

This chapter continues to address the issue of dynamical relations in the self-pattern by showing that the dynamics of a self-pattern are reflected in three significant and interrelated ways that allow for investigation. First, a self-pattern is reflectively reiterated in its narrative component. Second, studies of psychiatric or neurological disorders, including borderline personality disorder, schizophrenia, Alzheimer’s disease, and obsessive compulsive disorder can help us understand the precise nature of the dynamical relations in a self-pattern, and how they can fail. Third, referencing predictive processing accounts, neuroscience can also help to explicate, in a non-reductionist way, the dynamical relations that constitute the self-pattern. Discussions of the phenomenology of regret, depersonalization, and major depressive disorder help to flesh out the analysis.
The Cruel and Unusual Phenomenologies of Torture and Solitary Confinement
Authors: Gallagher Shaun
Published: December 2023

This chapter explores how violent practices (by individuals and by institutions) can lead to trauma and psychiatric illness. It explores extreme cases in which the trauma is so severe that there is a complete breakdown of the self-pattern, especially where breakdowns involve failures and distortions of intersubjective processes, namely in trauma associated with torture and the penal practice of solitary confinement. Phenomenological accounts of torture start with a focus on bodily processes involved in such experiences. The analysis can be broadened by considering the effects of violent trauma on the self-pattern as a whole. In this respect the importance of intersubjective processes will come into view. Likewise, solitary confinement, which excludes the individual from intersubjective interaction, is one that completely disrupts the self-pattern, the effects of which can manifest as extreme psychiatric disorders such as depersonalization and derealization.
Process
Authors: Jha Vyoma
Published: December 2023

This chapter examines the creation of the ISA—a new international organization led by India and backed primarily by developing countries—from the inception phase until it became a legal entity. Official documents and wide-ranging interview access provide data that offers insights into the treaty-making process. This chapter analyses the politico-legal issues behind the scenes in order to explain the creation of ISA as a treaty-based international organization. It lays down the analytical framework for the book’s main argument that the legal form of the ISA marked an innovation in the structure of international organizations that is best described as ‘soft law in a hard shell’: it uses the legal infrastructure of a treaty while relying on the social structure of participating actors for its future implementation. Empirical evidence suggests that three factors explain the treaty structure of the ISA: first, India’s lead role in driving the treaty-making process; second, the early involvement of non-state actors in implementation; and third, the value of legal form for developing countries.
Pigs
Authors: Taylor Colleen
Published: December 2023

Pigs’ natural adaptability, intelligence, affection, cleanliness, cohabitation with humans, and ability to convert almost anything into fat-storing calories contributed to the survival of the eighteenth-century peasantry under restricted civil and agricultural rights. Nevertheless, the Irish were racialized as pigs in English discourse dating back to the medieval era, and especially throughout the eighteenth and nineteenth centuries. Jonathan Swift’s A Modest Proposal famously deconstructs this racial and colonial similitude between pig body and Irish body, exposing the speciesist foundation of British imperialism. While the literary tradition of learned pigs in Britain ultimately affirmed human superiority over the degraded pig, the Irish language’s invocation of the pig suggests an ethos of respect, as in Scéala Mucce Meic Dathó, and poems by Aogán Ó Rathaille and anonymous eighteenth-century laments. Finally, William Carleton’s Traits and Stories of the Irish Peasantry (1833) celebrates the subversive and satiric potentials of human–pig collaboration when an Irish peasant and his sow dupe an elite English society.
A revolution in the juridical field
Authors: Baczko Adam
Published: December 2023

The formation of the Taliban insurgency’s juridical system harked back to the clerical movement’s beginnings in the context of the war in the 1980–90s. The uprising fomented by the Communist coup d’état of 1978 brought with it, in parallel with the armed strife, a revolution in the juridical field. The confrontations between the Communist regime and the mujahideen, followed by the struggle among commanders during the 1990s, led to the emergence of competing legal systems. The war for control of the state was compounded by ulama, Kabul University graduates, and notables competing to craft the law, a process that ended up consolidating religious legitimacy. Far from the archaism and irrationality commonly attributed to the Taliban, the movement organized around ulama entering the juridical and political fields. The structuring of the Taliban around jurists and aspiring jurists translated into a legal and moral vision of politics, an insistence on the restoration of law and order that aimed to put an end to deviance and disorder and thus to war.
Judges as an instrument of centralization
Authors: Baczko Adam
Published: December 2023

The Taliban judicial system was one of the elements of a broader administration, which incorporated the formal principles of state functioning. Within this clandestine government, Taliban judges were part of a system of cross-recognition and legitimization based on a differentiation between political, military, and judicial functions. Taliban leaders employed judges to buttress the hierarchy within the movement and thus maintain a centralized authority. However, judges depended on combatants to carry out their activities in their jurisdiction, which transferred to the relationship between leaders and commanders the latter’s respect for judicial authority. But while subordinate commanders were forced to close ranks, the most important ones had the means to resist, forcing the political leadership of the movement to make deals. The Taliban exemplified the problems posed by the differentiation of civilian and military functions in war. The relative autonomy of the judicial system was part of a cross-legitimization between fields. In return for recognizing the judge, which reinforced the magistrate’s credibility, the commander obtained a legal grounding for his action. In practice, however, wartime conditions placed constraints on the autonomy of judges and their ability to legitimize the commanders.
“Thai Nurses’ and Midwives’ Perceptions Regarding Barriers, Facilitators, and Competence in Neonatal Pain Management”
Authors: Mala Onanong , Forster Elizabeth M. , Kain Victoria J.
Published: December 2023

Background:

Effective neonatal pain management is reliant upon the expert care of nurses and midwives working in neonatal intensive care units (NICUs). Previous research has explored barriers, facilitators, and some aspects of nurse competence in managing neonatal pain; however, this research has been predominantly performed in Western countries. To date, little is known about the barriers, facilitators, and perceived competence of Thai nurses and midwives in relation to neonatal pain management in NICUs. Exploring Thai nurses’ and midwives’ perceptions in these areas is crucial for understanding the contextual nuances of neonatal pain management, which can guide the provision of care for these high-risk neonates.

Purpose:

To investigate nurses’ and midwives’ perceptions of barriers, facilitators, and competence regarding effective neonatal pain management in Thai NICUs.

Methods:

Data were collected using virtual one-to-one, semistructured interviews with 12 neonatal nurses and midwives between July and August 2021 in 3 units of 2 tertiary hospitals in Southern Thailand. Inductive thematic analysis was used to examine interview data.

Results:

These data revealed following 3 major themes: (a) barriers to effective neonatal pain management, (b) facilitators of effective neonatal pain management, and (c) perceptions of competence.

Implications for Practice:

Assisting nurses and midwives in overcoming barriers and strengthening facilitators while enhancing their competence may result in better neonatal pain management.

Implications for Research:

This study adds to our understanding that further research is needed to develop the interventions designed to change at individual, unit, and organizational levels, particularly implementing parent-friendly visitation and ongoing professional development in neonatal pain management.
Coronavirus Disease 2019 (COVID-19) and Venous Thromboembolism During Pregnancy and Postpartum
Authors: Bruno Ann M. , Horns Joshua J. , Metz Torri D.
Published: December 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk for macro- and micro-thrombi. Consensus guidelines recommend use of thromboprophylaxis in nonobstetric patients with SARS-CoV-2 infection admitted to the hospital. National-level studies evaluating venous thromboembolism (VTE) among pregnant and postpartum individuals with and without SARS-CoV-2 infection have not been completed. We performed a retrospective cohort study of individuals aged 18 years or older delivering at more than 20 weeks of gestation with data in the MarketScan Commercial Insurance Database from 2016 through 2020. Of 811,008 deliveries, SARS-CoV-2 infection during pregnancy or through 6 weeks postpartum was associated with increased risk for VTE compared with no infection (1.0% vs 0.5%, adjusted hazard ratio 2.62, 95% CI 1.60–4.29). Findings support further consideration of thromboprophylaxis in the obstetric population with SARS-CoV-2 infection.
The VANCO Trial Findings Are Generalizable to a North American Trauma Registry
Authors: Patterson Joseph T. , Slobogean Gerard P. , Gary Joshua L. , Castillo Renan C. , Firoozabadi Reza , Carlini Anthony R. , Joshi Manjari , Allen Lauren E. , Huang Yanjie , Bosse Michael J. , Obremskey William T. , McKinley Todd O. , Reid J. Spence , O'Toole Robert V. , O'Hara Nathan N. ,   and METRC
Published: December 2023

OBJECTIVES:

To estimate the generalizability of treatment effects observed in the VANCO trial to a broader population of patients with tibial plateau or pilon fractures.

METHODS:

Design and Setting: Clinical trial data from 36 United States trauma centers and Trauma Quality Programs registry data from more than 875 Level I–III trauma centers in the United States and Canada.

Patient Selection Criteria: Patients enrolled in the VANCO trial treated with intrawound vancomycin powder from January 2015 to June 2017 and 31,924 VANCO-eligible TQP patients admitted in 2019 with tibial plateau and pilon fractures.

Outcome Measure and Comparisons:
Deep surgical site infection and gram-positive deep surgical site infection estimated in the TQP sample weighed by the inverse probability of trial participation.

RESULTS:

The 980 patients in the VANCO trial were highly representative of 31,924 TQP VANCO-eligible patients (Tipton generalizability index 0.96). It was estimated that intrawound vancomycin powder reduced the odds of deep surgical infection by odds ratio (OR) = 0.46 (95% confidence interval [CI] 0.25–0.86) and gram-positive deep surgical infection by OR = 0.39 (95% CI, 0.18–0.84) within the TQP sample of VANCO-eligible patients. For reference, the trial average treatment effects for deep surgical infection and gram-positive deep surgical infection were OR = 0.60 (95% CI, 0.37–0.98) and OR = 0.44 (95% CI, 0.23–0.80), respectively.

CONCLUSIONS:

This generalizability analysis found that the inferences of the VANCO trial generalize and might even underestimate the effects of intrawound vancomycin powder when observed in a wider population of patients with tibial plateau and pilon fractures.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Single-Level Anterolateral and Posterior Interbody Fusion Techniques are Associated With Equivalent Long-Term Lumbar Reoperations
Authors: Narendran Nakul , Nilssen Paal K. , Skaggs David L. , Kim Sang D. , Perry Tiffany G. , Mikhail Christopher M. , Tuchman Alexander
Published: December 2023

Study Design.

Retrospective cohort study.

Objective.

This study compares reoperation rates and complications following single-level anterior lumbar interbody fusion (ALIF)/lateral lumbar interbody fusion (LLIF) and transforaminal lumbar interbody fusion (TLIF)/posterior lumbar interbody fusion (PLIF).

Summary of Background Data.

ALIF, LLIF, TLIF, and PLIF are widely used for degenerative disc disease. Lumbar interbody fusions have high rates of reoperation, primarily related to adjacent segment pathology and pseudarthrosis.

Materials and Methods.

The PearlDiver database was queried for patients (2010–2021) who had single-level ALIF/LLIF or TLIF/PLIF with same-day, single-level posterior instrumentation. ALIF/LLIF were combined, and similarly, TLIF/PLIF were combined, given how these operations are indistinguishable from Current Procedural Terminology coding. All patients were followed for ≥2 years and excluded if they had spinal traumas, fractures, infections, or neoplasms before surgery. The two cohorts, ALIF/LLIF and TLIF/PLIF, were matched 1:1 based on age, sex, Elixhauser-comorbidity index, smoking status, and diabetes. The primary outcome was the incidence of all-cause subsequent lumbar operations. Secondary outcomes included 90-day surgical complications.

Results.

After 1:1 matching, each cohort contained 14,070 patients. All-cause subsequent lumbar operations were nearly identical at five-year follow-up (9.4% ALIF/LLIFvs.9.5% TLIF/PLIF,P=0.91). Survival analysis using all-cause subsequent lumbar operations as the endpoint showed an equivalent 10-year survival rate of 86.0% (95%CI: 85.2-86.8). Within 90 days, TLIF/PLIF had more infections (1.3%vs.1.7%,P=0.007) and dural injuries (0.2%vs.0.4%,P=0.001). There was no difference in wound dehiscence, hardware complications, or medical complications.

Conclusion.

As utilized in real-world clinical practice, single-level anterolateralversusposterior approaches for interbody fusion have no effect on long-term reoperation rates.
Impact of Various Estimated Glomerular Filtration Rate Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults
Authors: Barreto Erin F. , Chang Jack , Rule Andrew D. , Mara Kristin C. , Meade Laurie A. , Paul Johar , Jannetto Paul J. , Athreya Arjun P. , Scheetz Marc H. ,   For the BLOOM Study Group
Published: December 2023

IMPORTANCE:

Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill.

OBJECTIVES:

This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance.

DESIGN, SETTING, AND PARTICIPANTS:

This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32).

MAIN OUTCOMES AND MEASURES:

A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations.

RESULTS:

The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias.

CONCLUSIONS AND RELEVANCE:

Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients.
Development and validation of a nomogram for elderly patients with ulcerative melanoma
Authors: Yan Jie , Wang Haiyan , Lu Xiaoou , Li Fengjuan
Published: December 2023

The current state of survival prediction models for elderly patients with ulcerative melanoma (uCM) is limited. We sought to develop a nomogram model that can predict overall survival of geriatric patients with uCM. The Surveillance, Epidemiology, and End Results (SEER) database served as a source for patients diagnosed with uCM between 2004 and 2015. Statistical analyses were conducted to determine the significant prognostic elements affecting overall survival using multivariate and univariate Cox proportional risk regression models. Subsequently, an independent forecasting nomogram was developed on the basis of these identified predictors. The predictive model was then assessed and validated through the utilization of receiver operating characteristic curves, calibration curves as well as decision curves. The study included a total of 5019 participants. Univariate and multivariate analyses revealed age, sex, marital status, primary site, tumor size, N stage, M stage, histological type, and surgery were independent prognostic factors. A nomogram was developed using the findings from both univariate and multivariate Cox analyses (P < 0.05). The receiver operating characteristic curves, which vary over time, and the area under the curve (AUC) for the training and validation cohorts, demonstrated the nomogram’s strong discriminatory ability. Additionally, the calibration curves indicated satisfactory agreement between the predicted values from the nomogram and the practical outcomes observed in both cohorts. Furthermore, the decision curve analysis curves displayed favorable positive net gains at all times, when the critical value is most likely to occur. In this study, age, sex, marital status, primary site, tumor size, N stage, M stage, histologic type and surgery were determined as independent predictors for elderly patients with uCM. Then, a predictive model with good discriminatory ability was constructed to predict 12-, 24-, and 36-month overall survival in geriatric patients with uCM, which facilitates patients’ counseling and individualized medical decision.
Real-world management practices and characteristics of patients with advanced melanoma initiated on immuno-oncology or targeted therapy in the first-line setting during the period 2015–2018 in Greece. The ‘SUMMER’ study: a retrospective multicenter chart review project
Authors: Bafaloukos Dimitrios , Kouzis Panagiotis , Gouveris Panagiotis , Boukovinas Ioannis , Kalbakis Konstantinos , Baka Sofia , Kyriakakis Georgios , Moschou Despoina , Molfeta Aristea , Demiri Stamatia , Mavroudis Dimitrios , Spanoudi Filio , Dimitriadis Ioannis , Gogas Helen
Published: December 2023

This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings of Greece. This was a multicenter, retrospective chart review study. Eligible consented (unless deceased, for whom consent was waived by the hospital) patients were consecutively included by six oncology clinics. The look-back period extended from informed consent or death to initial melanoma diagnosis. Between 9 Junuary 2021 and 9 February 2022, 225 eligible patients (all Caucasians; 60.4% male; 35.6% diagnosed with de novo advanced melanoma) were included. At 1LT initiation, median age was 62.6 years; 2.7/6.7/90.7% of the patients had Stage IIIB/IIIC/IV disease and 9.3% were unresected. Most frequent metastatic sites were the lung (46.7%), non-regional nodes (33.8%), and liver (20.9%). Among patients, 98.2% had single primary melanoma, 45.6% had disease localized on the trunk, and 63.6% were BRAF-mutant. Of the patients, 45.3% initiated 1LT with an IO-based, 53.3% with a TT-based regimen, and three patients (1.3%) received TT-based followed by IO-based or vice versa. Most common 1LT patterns (frequency ≥10%) were BRAFi/MEKi combination (31.6%), anti-PD-1 monotherapy (25.3%), BRAFi monotherapy (21.8%), and anti-CTLA-4 monotherapy (17.8%). Most frequent regimens were Dabrafenib+Trametinib in 25.3%, and monotherapies with Pembrolizumab/Ipilimumab/Vemurafenib/Dabrafenib in 23.6/17.8/11.1/10.7% of patients, respectively. SUMMER provides RWE on 1LT strategies and profile of patients initiated 1L IO- or TT-based therapy in Greece during the 3-year index period.
Integrated Care for Pregnant and Parenting People With Substance Use
Authors: Klie Kaylin A. , Nagle-Yang Sarah , Zhao Lulu , Fringuello Melanie E.
Published: December 2023

Caring for pregnant people with substance use requires knowledge about specific substances used, treatment options, and an integrated, trauma-informed care team. This chapter will discuss crucial information for clinicians regarding evidence-based practice for screening, intervention, and ongoing support for pregnant people and their families impacted by substance use.
Differences in respiratory function, depressive symptoms and quality of life between patients with hereditary motor and sensory neuropathy and myotonic dystrophy undergoing maintenance rehabilitation
Authors: Lajlar Nika , Vidmar Gaj , Moharić Metka
Published: December 2023

Hereditary motor and sensory neuropathy (HMSN) and myotonic dystrophy (MD) are chronic neuromuscular diseases that cause progressive muscular impairment and impact patient’s quality of life. Conflicting findings in existing literature underscore the need for focussed research on specific health aspects in these patients. The aim of the study was to explore the differences in respiratory function, depressive symptoms and quality of life between patients with HMSN and MD undergoing maintenance rehabilitation. Our prospective observational study included 62 HMSN patients (median age 53.5, range 19–79 years; 38 women) and 50 MD patients (median age 54.0, range 18–77 years; 34 women) undergoing maintenance rehabilitation. They performed respiratory function tests (vital capacity, forced vital capacity, forced expiratory volume and peak expiratory flow) and respiratory muscle strength tests (maximum inspiratory pressure, maximum expiratory pressure and sniff nasal inspiratory force). The Center for Epidemiological Studies-Depression Scale was used to evaluate depression, and their health-related quality of life was assessed using the Quality of Life in Genetic Neuromuscular Disease Questionnaire. Using logistic regression, we examined group-difference in presence of depressive symptoms while accounting for age, symptoms duration, and marital status. Multiple linear regression was used to assess the difference in quality-of-life scores, adjusting for age, gender, and symptoms’ duration. The HMSN group achieved statistically significantly better results than the MD group on all respiratory measures (about 17% absolute difference in the respiratory function measures and 30% relative difference in the respiratory muscle strength measures on average). Both groups exhibited a high level of depression symptoms (HMSN 24%, MD 44%; estimated adjusted odds-ratio MD vs. HMSN 1.9, 95% CI 0.8–4.5, P = 0.127). We did not find a statistically significant difference between the groups regarding quality-of-life domains, though a trend towards better quality-of-life among the HMSN patients could be observed. The implication for future practice is that the MD patients would potentially benefit the most from targeted respiratory-rehabilitation interventions, and both groups could benefit from focussed mental-health interventions.
Unveiling the CAZyme repertoire of a sponge-derived Pseudoalteromonas sp. strain for the degradation of marine polysaccharides
Authors: de Oliveira Bruno Francesco Rodrigues , Jackson Stephen A. , Dobson Alan D. W. , Laport Marinella S.
Published: December 2023

Despite their well‐known importance to the holobiont homeostasis, carbohydrate‐active enzymes (CAZymes) from the sponge microbiome have to date been largely understudied from an industrial perspective. Enzymes that degrade marine polysaccharides (MPs) are receiving increasing attention as alternatives in the biorefinery sector and for use in the generation of high‐value‐added hydrolysis products. Screening of the agarolytic Pseudoalteromonas sp. strain PA2MD11, isolated from the Brazilian sponge Plakina cyanorosea, on selective media indicated that the strain degrades agarose, κ‐carrageenan and sodium alginate. Subsequently in silico analysis of the strain's genome indicated that around 3 % of the total genome encoded for CAZymes. These consisted mostly of glycoside hydrolases (GH) and glycosyltransferases (GT). Four agarase genes were also present, three from the family GH50 and one from the family GH16, with sequences from other free‐living and psychrophile Pseudoalteromonas genomes as its closest relatives. These agarases are structurally related to exo‐(GH50) and endo‐β‐agarases (GH16), and appear to encode for a complete agarolytic pathway. The two alginate lyases were classified as polysaccharide lyases (PL) from the families 6 and 17, with chondroitin‐ and heparin‐like domains, respectively, and shared common homologues sequences with an estuarine Pseudoalteromonas lipolytica strain. Data on the cloning and heterologous expression of these genes will be presented. To our knowledge, this is the first time that a “genome mining” based approach has been undertaken to identify these groups of MPs‐degrading CAZymes from cultivable members of the sponge microbiome.
Highly variable molecular signatures of TDP-43 loss of function are associated with nuclear pore complex injury in a population study of sporadic ALS patient iPSNs
Authors: Rothstein Jeffrey D. , Warlick Caroline , Coyne Alyssa N.
Published: December 2023

The nuclear depletion and cytoplasmic aggregation of the RNA binding protein TDP-43 is widely considered a pathological hallmark of Amyotrophic Lateral Sclerosis (ALS) and related neurodegenerative diseases. Recent studies have artificially reduced TDP-43 in wildtype human neurons to replicate loss of function associated events. Although this prior work has defined a number of gene expression and mRNA splicing changes that occur in a TDP-43 dependent manner, it is unclear how these alterations relate to authentic ALS where TDP-43 is not depleted from the cell but miscompartmentalized to variable extents. Here, in this population study, we generate ∼30,000 qRT-PCR data points spanning 20 genes in induced pluripotent stem cell (iPSC) derived neurons (iPSNs) from >150 control, C9orf72 ALS/FTD, and sALS patients to examine molecular signatures of TDP-43 dysfunction. This data set defines a time dependent and variable profile of individual molecular hallmarks of TDP-43 loss of function within and amongst individual patient lines. Importantly, nearly identical changes are observed in postmortem CNS tissues obtained from a subset of patients whose iPSNs were examined. Notably, these studies provide evidence that induction of nuclear pore complex (NPC) injury via reduction of the transmembrane Nup POM121 in wildtype iPSNs is sufficient to phenocopy disease associated signatured of TDP-43 loss of function thereby directly linking NPC integrity to TDP-43 loss of function. Therapeutically, we demonstrate that the expression ofallmRNA species associated with TDP-43 loss of function can be restored in sALS iPSNs via two independent methods to repair NPC injury. Collectively, this data 1) represents a substantial resource for the community to examine TDP-43 loss of function events in authentic sALS patient iPSNs, 2) demonstrates that patient derived iPSNs can accurately reflect actual TDP-43 associated alterations in patient brain, and 3) that targeting NPC injury events can be preclinically and reliably accomplished in an iPSN based platform of a sporadic disease.
Trigeminal nerve direct current stimulation causes sustained increase in neural activity in the rat hippocampus
Authors: Chen Liyi , Deng Zhengdao , Asamoah Boateng , Laughlin Myles Mc
Published: December 2023

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method that can modulate many brain functions including learning and memory. Recent evidence suggests that tDCS memory effects may be caused by co-stimulation of scalp nerves such as the trigeminal nerve (TN), and not the electric field in the brain. The TN gives input to brainstem nuclei, including the locus coeruleus that controls noradrenaline release across brain regions, including hippocampus. However, the effects of TN direct current stimulation (TN-DCS) are currently not well understood. In this study we hypothesized that TN-DCS manipulates hippocampal activity via an LC-noradrenergic bottom-up pathway. We recorded neural activity in rat hippocampus using multichannel silicon probes. We applied 3 minutes of 0.25 mA or 1 mA TN-DCS, monitored hippocampal activity for up to 1 hour and calculated spikes-rate and spike-field coherence metrics. Subcutaneous injections of xylocaine were used to block TN and intraperitoneal injection of clonidine to block the LC pathway. We found that 1 mA TN-DCS caused a significant increase in hippocampal spike-rate lasting 45 minutes in addition to significant changes in spike-field coherence, while 0.25 mA TN-DCS did not. TN blockage prevented spike-rate increases, confirming effects were not caused by the electric field in the brain. When 1 mA TN-DCS was delivered during clonidine blockage no increase in spike-rate was observed, suggesting an important role for the LC-noradrenergic pathway. These results provide a neural basis to support a tDCS TN co-stimulation mechanism. TN-DCS emerges as an important tool to potentially modulate learning and memory.

Highlights

Trigeminal nerve direct current stimulation (TN-DCS) boosts hippocampal spike rates

TN-DCS alters spike-field coherence in theta and gamma bands across the hippocampus.

Blockade experiments indicate that TN-DCS modulated hippocampal activity via the LC-noradrenergic pathway.

TN-DCS emerges as a potential tool for memory manipulation.

Figure Graphic Abstract
Sequential Optimal Experimental Design of Perturbation Screens Guided by Multi-modal Priors
Authors: Huang Kexin , Lopez Romain , Hütter Jan-Christian , Kudo Takamasa , Rios Antonio , Regev Aviv
Published: December 2023

Understanding a cell’s expression response to genetic perturbations helps to address important challenges in biology and medicine, including the function of gene circuits, discovery of therapeutic targets and cell reprogramming and engineering. In recent years, Perturb-seq, pooled genetic screens with single cell RNA-seq (scRNA-seq) readouts, has emerged as a common method to collect such data. However, irrespective of technological advances, because combinations of gene perturbations can have unpredictable, non-additive effects, the number of experimental configurations far exceeds experimental capacity, and for certain cases, the number of available cells. While recent machine learning models, trained on existing Perturb-seq data sets, can predict perturbation outcomes with some degree of accuracy, they are currently limited by sub-optimal training set selection and the small number of cell contexts of training data, leading to poor predictions for unexplored parts of perturbation space. As biologists deploy Perturb-seq across diverse biological systems, there is an enormous need for algorithms to guide iterative experiments while exploring the large space of possible perturbations and their combinations. Here, we propose a sequential approach for designing Perturb-seq experiments that uses the model to strategically select the most informative perturbations at each step for subsequent experiments. This enables a significantly more efficient exploration of the perturbation space, while predicting the effect of the rest of the unseen perturbations with high-fidelity. Analysis of a previous large-scale Perturb-seq experiment reveals that our setting is severely restricted by the number of examples and rounds, falling into a non-conventional active learning regime called “active learning on a budget”. Motivated by this insight, we develop IterPert, a novel active learning method that exploits rich and multi-modal prior knowledge in order to efficiently guide the selection of subsequent perturbations. Using prior knowledge for this task is novel, and crucial for successful active learning on a budget. We validate IterPertusing insilico benchmarking of active learning, constructed from a large-scale CRISPRi Perturb-seq data set. We find that IterPertoutperforms other active learning strategies by reaching comparable accuracy at only a third of the number of perturbations profiled as the next best method. Overall, our results demonstrate the potential of sequentially designing perturbation screens through IterPert.
Comparison of chronic aerosol inhalation with combustible cigarette and e-cigarette on the psychiatric behaviors and neuroimmune profile in mice
Authors: Xu Zhibin , Ren Jiayan , Jing Xiaoyuan , Mo Zhi-zhun , Li Zixuan , Zhao Yiqing , Wang Ruoxi , Wu Zehong , Jiang Xin-tao , Tian Ye , Wang Liping , Chen Zuxin , Liu Xin-an
Published: December 2023

With the worldwide use of electronic cigarettes (e-cigarettes) as a substitution for tobacco, the effects of e-cigarette vapor exposure on human health have been investigated. However, the comparison of long-term effects of aerosol inhalation with combustible cigarette and e-cigarette on the psychiatric behaviors has not been fully revealed. The present study examines the distinct effects of combustible cigarette and e-cigarette on anxiety, depression, cognition, and social behaviors. Here we found that the combustible cigarette induced the higher level of anxiety after long-term inhalation compared to the e-cigarettes with or without the tobacco flavor. Since the mechanism of action on the psychiatric behaviors entails the alterations on the neuroimmune-sensors and principal regulators such as glial cells, we further profiled the alterations of microglia and astrocytes by chronic inhalation of combustible tobacco cigarette, specifically the negative correlations between the IBA-1 level in the locus coeruleus (LC) and the latency to nest in VLT; as well as the GFAP level in LC and the open arm time in EPM were observed. Our current data provided an insight into the less impact of e-cigarettes on the anxiety-like behaviors and neuroimmune activation compared to combustible tobacco cigarettes which is not related to the flavor in e-cigarette, and the modulation on the neuroimmune signals in LC could be a therapeutic target for smoking-related anxiety.
Deep learning to overcome Zernike phase-contrast nanoCT artifacts for automated micro-nano porosity segmentation in bone
Authors: Silveira Andreia , Greving Imke , Longo Elena , Scheel Mario , Weitkamp Timm , Fleck Claudia , Shahar Ron , Zaslansky Paul
Published: December 2023

Bone material contains a hierarchical network of micro- and nano-cavities and channels, known as the lacuna-canalicular network (LCN), that is thought to play an important role in mechanobiology and turnover. The LCN comprises micrometer-sized lacunae, voids that house osteocytes, and submicrometer-sized canaliculi that connect bone cells. Characterization of this network in three dimensions is crucial for many bone studies. To quantify X-ray Zernike phase-contrast nanotomography data, deep learning is used to isolate and assess porosity in artifact-laden tomographies of zebrafish bones. A technical solution is proposed to overcome the halo and shade-off domains in order to reliably obtain the distribution and morphology of the LCN in the tomographic data. Convolutional neural network (CNN) models are utilized with increasing numbers of images, repeatedly validated by `error loss' and `accuracy' metrics. U-Net and Sensor3D CNN models were trained on data obtained from two different synchrotron Zernike phase-contrast transmission X-ray microscopes, the ANATOMIX beamline at SOLEIL (Paris, France) and the P05 beamline at PETRA III (Hamburg, Germany). The Sensor3D CNN model with a smaller batch size of 32 and a training data size of 70 images showed the best performance (accuracy 0.983 and error loss 0.032). The analysis procedures, validated by comparison with human-identified ground-truth images, correctly identified the voids within the bone matrix. This proposed approach may have further application to classify structures in volumetric images that contain non-linear artifacts that degrade image quality and hinder feature identification.
Way leaves, rights of way and ducting policies for 5G mobile network deployment in India using international best practices
Authors: Mitra Anuradha , Sridhar V. , Sarangi Gopal K.
Published: December 2023

Purpose

This paper aims to draw lessons for telecommunications (telecom) network deployment in India, from a study of policy and regulatory approaches taken by other federal administrations in streamlining processes for site clearances, grant of rights of way (RoW) and approvals for local infrastructure deployment and sharing. With the urgent need for setting up small cells and rapid fiberisation of networks in the 5G era, the importance of such processes has gained prominence.

Design/methodology/approach

The authors adopt qualitative thematic content analysis with three-tier coding and classification to identify themes in archival and current documentary data and information obtained from subject-matter experts in the countries studied.

Findings

Formulation and implementation of telecom policy is led by national governments. However, national telecom administrations, in recognition of new needs, have co-opted states and local authorities as partners in development of telecom networks, providing the overall framework, guidance and appropriate incentives where required.

Practical implications

This cooperative model could work well in India, where telecom policy making and regulation is the prerogative of the central government, but administration of RoW and local clearances for cable laying, tower siting and associated infrastructure activities for expanding telecom networks are left to decentralised decision-making in the states and local bodies.

Originality/value

This research attempts to sytematise, thematise and draw cross-country comparisons to inform regulatory and administrative policy for 5G infrastructure rollout in India.
Spillover effect of foreign direct investment on wage-inequality in Indian manufacturing industries
Authors: Gupta Arpit , Chand Arya Kumar Srustidhar
Published: December 2023

Purpose

The purpose of this paper is to study the spillover effects of foreign direct investment (FDI) on skilled–unskilled wage inequality in the Indian manufacturing industries.

Design/methodology/approach

The authors show theoretically with a model of spillover that if foreign firms (receiving FDI) have a negative spillover effect on domestic firms (not receiving FDI), then the level of capital and skilled workers in the domestic firms falls down. Consequently, the authors conduct an empirical analysis by using system GMM estimation technique on the firm-level data of the Indian organised manufacturing sector.

Findings

The authors show that wage inequality worsens when there is negative spillover effects like competition spillover or skill spillover effect of FDI in India.

Originality/value

To the best of the authors’ knowledge, this is the first attempt to measure the various spillover effects of FDI on the wage inequality in the Indian manufacturing industries by using firm-level data.
The adoption of evidence-based policing: the pivotal role of first-line police leaders across England and Wales
Authors: Pepper Ian , Rogers Colin , Turner James
Published: December 2023

Purpose

First-line leaders across the emergency services are instrumental in leading the development of a workforce fit to face current and future challenges. As such in addition to utilising their specific craft, leaders need to be equipped to understand and apply evidence-based practices. With a focus on first-line leadership in policing, this paper will have both national and international resonance for those organisations attempting to embed an evidence-based culture.

Design/methodology/approach

The paper utilises a review of literature to develop a viewpoint identifying challenges and benefits of the adoption of evidence-based policing (EBP) by first-line leaders.

Findings

First-line leaders, whether police officers, police staff or volunteers, require opportunities to develop their own knowledge, understanding and skills of applying EBP in the workplace. Acknowledging challenges exist in the widespread adoption of EBP, such learning, at the appropriate educational level, will enable leaders to effectively champion the adoption of EBP, informing both their own decision-making and professional practices as well as those across their teams.

Practical implications

The first-line leader role is highly influential, as such, it is essential that these leaders develop their knowledge, understanding and application of EBP in the workplace in order to lead the expected cultural change.

Originality/value

This paper provides a current framework for the understanding of the context and potential impact of educationally levelled formal leadership learning required to champion the broad adoption of EBP across policing.