bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons for global microfinance from . . . the United States?
Authors: Klein Joyce , Ogden Timothy
Published: December 2023

Questions about the future of global microfinance, and specifically the future of policy and subsidy for microfinance, abounded even before the pandemic. Competing policy priorities and limited budgets mean key questions must be answered. How should funders and policy-makers approach subsidy to sustain or increase the reach of microfinance? How do policy-makers find a balance between consumer protection and minimizing the costs of regulation for providers who attempt to serve low-income (and often unprofitable) customers? Can technology be a solution to long-standing challenges, increasing reach and lowering costs? Insight into these questions can be gained from an unlikely place: the United States. For decades, global microfinance advocates have suggested the US has much to learn from the innovations and successes of the global microfinance movement. However, the financial system in the US is best understood not as the result of an absence of microfinance, but an example of how a financial system evolves, and the enduring challenges, even when it includes microfinance. Microfinance has been historically present in the United States, since at least Benjamin Franklin, and extending through the present. A clear-eyed and informed view of that history provides several important lessons, including the necessity for on-going subsidy, the never-ending challenge of consumer protection, the rising costs that can come with robust market competition, and the inability of technology to fix systemic challenges. Policy-makers and funders the world over can benefit from learning from each other, particularly if the conversations start from a different point: the challenges are shared and fruitful ideas and valuable lessons can come from all parties.
Rice transcription factor OsNAC2 maintains the homeostasis of immune responses to bacterial blight
Authors: Zhong Qun , Yu Jiangtao , Wu Yiding , Yao Xuefeng , Mao Chanjuan , Meng Xiangzong , Ming Feng
Published: December 2023

Rice (Oryza sativa) bacterial blight, caused by Xanthomonas oryzae pv. Oryzae (Xoo), threatens plant growth and yield. However, the molecular mechanisms underlying rice immunity against Xoo remain elusive. Here, we identified a NAC (NAM-ATAF-CUC) transcription factor OsNAC2 as a negative regulator in the resistance to bacterial blight disease in rice. Constitutive overexpression of OsNAC2 inhibited the expression of salicylic acid (SA) biosynthesis-related genes (i.e. isochorismate synthase 1 (OsICS1), phenylalanine ammonia lyase 3 (OsPAL3), etc.) with adverse impacts on the pathogenesis-related proteins (PRs) responses and compromised blight resistance. Moreover, OsNAC2 interacted with APETALA2/ethylene-responsive element binding protein (AP2/EREBP) transcription factor OsEREBP1 and possibly threatened its protein stability, destroying the favorable interaction of OsEREBP1–Xa21-binding protein OsXb22a in the cytoplasm during Xoo-induced infection. On the contrary, downregulation of OsNAC2 resulted in enhanced resistance to bacterial blight in rice without any growth or yield penalties. Our results demonstrated that OsNAC2 inhibits SA signaling and stably interacted with OsEREBP1 to impair disease resistance. This OsNAC2-OsEREBP1-based homeostatic mechanism provided insights into the competition between rice and bacterial pathogens, and it will be useful to improve the disease resistance of important crops through breeding.
Education and learning: potential methodological and ethical issues in systematic reviews containing a meta-analysis: some critical reading suggestions for junior doctors
Authors: Faggion Clovis Mariano
Published: December 2023

Junior doctors make clinical decisions regularly; therefore, they need to adequately interpret the evidence supporting these decisions. Patients can be harmed if clinical treatments are supported by biased or unreliable evidence. Systematic reviews that contain meta-analyses of randomized controlled trials are a relatively low-biased type of evidence to support clinical interventions. Therefore, it is reasonable to think that doctors will likely select this type of study to answer clinical questions. In this article, doctors are informed about potential methodological and ethical issues in systematic reviews that contain a meta-analysis that are sometimes not easily identified or even overlooked by the current tools developed to assess their methodological quality or risk of bias. The article presents a discussion of topics related to data extraction, accuracy in reporting, reproducibility, heterogeneity, quality assessment of primary studies included in the systematic review, sponsorship, and conflict of interest. It is expected that the information reported will be useful for junior doctors when they are reading and interpreting evidence from systematic reviews containing meta-analyses of therapeutic interventions, mainly those doctors unfamiliar with methodological principles.
Hydrogen-rich water improves sleep consolidation and enhances forebrain neuronal activation in mice
Authors: Vincent Scott M , Madani Melika , Dikeman Dante , Golden Kyle , Crocker Naomi , Jackson Cameron , Wimmer Sam P , Dover Mary , Tucker Alexis , Ghiani Cristina A , Colwell Christopher S , LeBaron Tyler W , Tarnava Alex , Paul Ketema N
Published: December 2023

Study Objectives

Sleep loss contributes to various health issues and impairs neurological function. Molecular hydrogen has recently gained popularity as a nontoxic ergogenic and health promoter. The effect of molecular hydrogen on sleep and sleep-related neural systems remains unexplored. This study investigates the impact of hydrogen-rich water (HRW) on sleep behavior and neuronal activation in sleep-deprived mice.

Methods

Adult C57BL/6J mice were implanted with electroencephalography (EEG) and electromyography (EMG) recording electrodes and given HRW (0.7–1.4 mM) or regular water for 7 days ad libitum. Sleep–wake cycles were recorded under baseline conditions and after acute sleep loss. Neuronal activation in sleep- and wake-related regions was assessed using cFos immunostaining.

Results

HRW increased sleep consolidation in undisturbed mice and increased non-rapid-eye movement and rapid-eye-movement sleep amount in sleep-deprived mice. HRW also decreased the average amount of time for mice to fall asleep after light onset. Neuronal activation in the lateral septum, medial septum, ventrolateral preoptic area, and median preoptic area was significantly altered in all mice treated with HRW.

Conclusions

HRW improves sleep consolidation and increases neuronal activation in sleep-related brain regions. It may serve as a simple, effective treatment to improve recovery after sleep loss.
ISX-9 Promotes KGF Secretion From MSCs to Alleviate ALI Through NGFR-ERK-TAU-β-Catenin Signaling Axis
Authors: Tian Yi , Deng Qinyi , Yang Xiaotong , Wang Chen , Minh Le Van , Ji Ri , Liang Xin , Feng Yun
Published: December 2023

Background

Mesenchymal stem cells (MSCs) have been widely studied to alleviate acute lung injury (ALI) due to their paracrine function. However, the microenvironment of inflammatory outbreaks significantly restricted the factors secreted from MSCs like keratinocyte growth factor (KGF). KGF is a growth factor with tissue-repaired ability. Is there a better therapeutic prospect for MSCs in combination with compounds that promote their paracrine function? Through compound screening, we screened out isoxazole-9 (ISX-9) to promote MSCs derived KGF secretion and investigated the underlying mechanisms of action.

Methods

Compounds that promote KGF secretion were screened by a dual-luciferase reporter gene assay. The TMT isotope labeling quantitative technique was used to detect the differential proteins upon ISX-9 administrated to MSCs. The expressions of NGFR, ERK, TAU, and β-catenin were detected by Western blot. In the ALI model, we measured the inflammatory changes by HE staining, SOD content detection, RT-qPCR, immunofluorescence, etc. The influence of ISX-9 on the residence time of MSCs transplantation was explored by optical in vivo imaging.

Results

We found out that ISX-9 can promote the expression of KGF in MSCs. ISX-9 acted on the membrane receptor protein NGFR, upregulated phosphorylation of downstream signaling proteins ERK and TAU, downregulated phosphorylation of β-catenin, and accelerated β-catenin into the nucleus to further increase the expression of KGF. In the ALI model, combined ISX-9 with MSCs treatments upgraded the expression of KGF in the lung, and enhanced the effect of MSCs in reducing inflammation and repairing lung damage compared with MSCs alone.

Conclusions

ISX-9 facilitated the secretion of KGF from MSCs both in vivo and in vitro. The combination of ISX-9 with MSCs enhanced the paracrine function and anti-inflammatory effect of MSCs compared with MSCs applied alone in ALI. ISX-9 played a contributive role in the transplantation of MSCs for the treatment of ALI.
Direct Reprogramming of Fibroblasts to Osteoblasts: Techniques and Methodologies
Authors: Fallah Asghar , Beke Alexander , Oborn Connor , Soltys Carrie-Lynn , Kannu Peter
Published: December 2023

Direct reprogramming (DR) is an emerging technique that can be applied to convert fibroblasts into osteoblast-like cells, promoting bone formation and regeneration. We review the current methodology of DR in relation to the creation of induced osteoblasts, including a comparison of transcription factor-mediated reprogramming and nontranscription factor-mediated reprogramming. We review the selection of reprogramming factors and delivery systems required. Transcription factor cocktails, such as the RXOL cocktail (Runx2, Osx, OCT3/4, and L-MYC), have shown promise in inducing osteogenic differentiation in fibroblasts. Alterations to the original cocktail, such as the addition of Oct9 and N-myc, have resulted in improved reprogramming efficiency. Transcription factor delivery includes integrative and nonintegrative systems which encompass viral vectors and nonviral methods such as synthetic RNA. Recently, an integrative approach using self-replicating RNA has been developed to achieve a longer and more sustained transcription factor expression. Nontranscription factor-mediated reprogramming using small molecules, proteins, inhibitors, and agonists has also been explored. For example, IGFBP7 protein supplementation and ALK5i-II inhibitor treatment have shown potential in enhancing osteoblast reprogramming. Direct reprogramming methods hold great promise for advancing bone regeneration and tissue repair, providing a potential therapeutic approach for fracture healing and the repair of bone defects. Multiple obstacles and constraints need to be addressed before a clinically significant level of cell therapy will be reached. Further research is needed to optimize the efficiency of the reprogramming cocktails, delivery methods, and safety profile of the reprogramming process.
Implementation science for cancer control: One center’s experience addressing context, adaptation, equity, and sustainment
Authors: Glasgow Russell E , Ford Bryan S , Bradley Cathy J
Published: December 2023

Implementation science (IS) has great potential to enhance the frequency, speed, and quality of the translation of evidence-based programs, policies, products, and guidelines into practice. Progress has been made, but with some notable exceptions, this promise has not been achieved for cancer prevention and control. We discuss five interrelated but conceptually distinct, crosscutting issues important to accelerate IS for cancer prevention and control and how our Colorado Implementation Science Center in Cancer Control (COISC3) addressed these issues. These needs and opportunities include more fully addressing changing, multi-level context; guiding rapid, iterative adaptations; evaluating innovative approaches to engagement and health equity; greater attention to costs and economic issues; and sustainability. We summarize conceptual issues; evaluation needs and capacity building activities and then provide examples of how our IS center addressed these five needs for cancer prevention and control. We discuss changes made to address priorities of (i) guiding adaptations of implementation strategies to address changing context and (ii) working on issues identified and prioritized by our primary care partners rather than the research team. We conclude with discussion of lessons learned, limitations, and directions for future research and practice in IS to enhance cancer prevention and control as well as translational behavioral medicine more generally.
Using Behaviour Change Techniques to characterize patient educational interventions in tertiary individual prevention of work-related skin diseases
Authors: Ristow Nele , Rocholl Marc , Wilke Annika , John Swen Malte , Ludewig Michaela
Published: December 2023

Tertiary Individual Prevention is an interprofessional inpatient rehabilitation programme offered to workers affected by work-related skin diseases. Health educational interventions aiming at changing skin protection behaviour are a pivotal component of the programme. This paper aims at characterizing the content of the educational interventions of the interprofessional inpatient rehabilitation programme and at reporting the mechanisms and functions for behaviour change. We retrospectively analysed existing health educational interventions with document analyses and field observations. The intervention was described using the Template of Intervention Description and Replication (TIDieR). For the intervention content, the Behaviour Change Technique (BCT) Taxonomy (v1) was applied. To characterize the intervention in detail, the BCTs were then mapped to the intervention functions, the COM-B model (Capability, Opportunity, Motivation) and the Theoretical Domains Framework (TDF) from the Behaviour Change Wheel (BCW). The health educational interventions consist of seven components. Five are delivered in a group and two as tailored face-to-face counselling. We identified 23 BCTs in 10 groups. The most common used BCTs are “instruction on how to perform skin protection behaviour,” “salience of consequences,” “information about skin health,” and “demonstration of skin protection behaviour.” To initiate the process of behaviour change in skin protection behaviour by the individuals, changes are required in all three behavioural sources (Capability, Opportunity, Motivation) and primarily in the theoretical constructs “behavioural regulation,” “skills,” and “beliefs about consequences.” For this purpose, the five intervention functions “enablement,” “training,” “education,” “modelling,” and “persuasion” are used. Health educational interventions to change skin protection behaviour consists of different BCTs, mechanisms of change and intervention functions. This work helps to better understand the mechanisms and means of behaviour change and enables replication in other settings. In the future, the intervention programme should be extended to include BCTs addressing domains for behaviour changes which have not yet been included to maintain the new behaviour in the long-term. Finally, we recommend to report more elements of the rehabilitation programme (e.g. psychological interventions) in a standardized manner by frameworks used in this paper.
The Relationship between Climate Action and Poverty Reduction
Authors: Lankes Hans Peter , Macquarie Rob , Soubeyran Éléonore , Stern Nicholas
Published: December 2023

There is growing awareness that actions by policymakers and international organizations to reduce poverty, and those to mitigate and adapt to climate change, are inextricably linked and interwoven. This paper examines relevant academic and policy literature and evidence on this relationship and explores the potential for a new form of development that simultaneously mitigates climate change, manages its impacts, and improves the wellbeing of people in poverty. First, as a key foundation, it outlines the backdrop in basic moral philosophy, noting that climate action and poverty reduction can be motivated both by a core principle based on the right to development and by the conventional consequentialism that is standard in economics. Second, it reviews assessments of the current and potential future impacts of weakly managed climate change on the wellbeing of those in poverty, paying attention to unequal effects, including by gender. Third, it examines arguments and literature on the economic impacts of climate action and policies and how those affect the wellbeing of people in poverty, highlighting the importance of market failures, technological change, systemic dynamics of transition, and distributional effects of mitigation and adaptation. Finally, the paper surveys the current state of knowledge and understanding of how climate action and poverty reduction can be integrated in policy design, indicating where further research can contribute to a transition that succeeds in both objectives.
A scientist’s guide to Solifugae: how solifuges could advance research in ecology, evolution, and behaviour
Authors: Hebets Eileen A , Oviedo-Diego Mariela , Cargnelutti Franco , Bollatti Fedra , Calbacho-Rosa Lucia , Mattoni Camilo I , Olivero Paola , Simian Catalina , Abregú Debora , Vrech David E , Peretti Alfredo V
Published: December 2023

Despite having >1200 described species and despite their nearly worldwide distribution and prevalence in many xeric ecosystems, relative to many other arachnid groups, we know little about the natural history and behaviour of animals in the order Solifugae (camel spiders, sun spiders, sun scorpions, etc.). Here, we review the current solifuge literature through the lens of conceptual research areas in ecology, evolution, and behaviour and propose ways in which solifuges can contribute to research in specific subfields, as follows: (i) ecology: community and trophic dynamics; connecting food webs; habitat specialization; and biodiversity and conservation; (ii) evolution: speciation and diversification; activity cycles and associated traits; adaptations for speed; and living in extreme environments; and (iii) behaviour and sensory systems: sleep, quiescence, and diapause; sensory systems and sensory ecology; learning and cognition; and mating systems, sexual selection, and sexual conflict. This resource can provide a starting point for identifying research programmes that will simultaneously contribute basic natural history information about this under-studied group and provide a broader understanding of fundamental concepts and theories across the life sciences. We hope that scientists will take this review as a challenge to develop creative ways of leveraging the unique features of solifuges to advance scientific knowledge and understanding.
Outcomes of Humerus Nonunion Surgery in Patients with Initial Operative Fracture Fixation
Authors: Harrison Noah , Hysong Alexander , Posey Samuel , Yu Ziqing , Chen Andrew T. , Pallitto Patrick , Gardner Michael , Dumpe Jarrod , Mir Hassan , Babcock Sharon , Natoli Roman M. , Adams John D. , Zura Robert D. , Miller Anna , Seymour Rachel B. , Hsu Joseph R. , Obremskey William ,   and the Evidence-Based Musculoskeletal Injury and Trauma Collective (EMIT)
Published: December 2023

OBJECTIVES:

To describe outcomes following humerus aseptic nonunion surgery in patients whose initial fracture was treated operatively and to identify risk factors for nonunion surgery failure in the same population.

METHODS

Design:

Retrospective Case series.

Setting:

Eight academic level-one trauma centers.

Patients Selection Criteria:

Patients with aseptic humerus nonunion (OTA/AO 11 and 12) after initial operative management between 1998 and 2019

Outcome Measures and Comparisons:

Success rate of nonunion surgery.

RESULTS:

90 patients were included (56% female; median age 50 years; mean follow up 21.2 months). Of 90 aseptic humerus nonunions, 71 (78.9%) united following nonunion surgery. 30 patients (33.3%) experienced one or more post-operative complications including infection, failure of fixation, and readmission. Multivariate analysis found that not performing revision internal fixation during nonunion surgery (n=8; p=0.002) and post-operative de-novo infection (n=9; p=0.005) were associated with an increased risk of recalcitrant nonunion. Patient smoking status and the use of bone graft were not associated with differences in the nonunion repair success rate.

CONCLUSIONS:

This series of previously-operated aseptic humerus nonunions found that over one in five patients failed nonunion repair. De-novo post-operative infection and failure to perform revision internal fixation during nonunion surgery were associated with recalcitrant nonunion. Smoking and use of bone graft did not influence the success rate of nonunion surgery. These findings can be used to give patients a realistic expectation of results and complications following humerus nonunion surgery.
Pedicled Peroneus Brevis Muscle Flaps As An Alternative to Fasciocutaneous Rotational Flaps For Lower Extremity Soft Tissue Defects
Authors: Antúnez Merlin , Huyen Cormac , Neiman Rafael
Published: December 2023

OBJECTIVE:

To report our experience using a peroneus brevis flap for soft tissue defects of the distal third of the tibia, ankle, and hindfoot in resource challenged environments.

METHODS:

Design:

Retrospective review

Setting:

Rural outpatient surgical facility in Honduras

Patient Selection Criteria:

Patients who sustained tibia, ankle, or hindfoot fractures or traumatic degloving, with critical sized soft tissue defects treated with either a proximally based or distally based pedicled peroneus brevis flap (PBF) to achieve coverage of the middle and distal third of the leg, ankle, and/or hindfoot.

Outcome Measures and Comparisons:

Flap healing, complications and re-operations.

RESULTS:

23 patients, four with proximally based and 19 with distally based PBF flaps were included. The mean patient age was 37.3 (SD = 18.3; range 18-75 years). Duration of follow up averaged 14.7 months (SD = 11.4; range 4-46). The PBF successfully covered the defect without the need for additional unplanned surgical flap coverage in all but two patients. Thirty percent of the PBFs received a split thickness skin graft, while the remainder granulated successfully without skin graft. Four flaps were partially debrided without additional flap mobilization, while one flap was lost completely. Ten patients had successful re-elevation of their flaps for secondary procedures such as implant removal, spacer exchange, deep debridements, and bone grafting. All donor site incisions healed without complication.

CONCLUSIONS:

The pedicled peroneus brevis flap allows coverage of distal leg, ankle, and hindfoot wounds using muscle in patients who may otherwise require free tissue flaps or transfer to another institution for coverage. Peroneus brevis flaps can be learned and implemented without the use of microvascular techniques.
Ultrasonographic Evaluation of Upper Esophageal Sphincter for Dysphagia During the Acute Postoperative Phase of Anterior Cervical Surgery
Authors: Obo Takuya , Nakano Atsushi , Fujishiro Takashi , Mizutani Masahiro , Nakaya Yoshiharu , Hayama Sachio , Usami Yoshitada , Neo Masashi
Published: December 2023

Study Design:

A retrospective study.

Objective:

To verify the pathophysiology of dysphagia during the acute postoperative phase of anterior cervical surgery and to identify its predictive features, using ultrasonographic (US) examination for upper esophageal sphincter (UES).

Summary of Background Data:

There are no clinical studies investigating dysphagia after anterior cervical surgery, using US examination for UES.

Materials and Methods:

We enrolled patients who underwent anterior cervical spine surgery between August 2018 and March 2022. Dysphagia was evaluated using the Eating Assessment Tool-10 (EAT-10) questionnaires. The US examination was performed preoperatively and 2 weeks postoperatively. Three US parameters for morphologic measurements (outer diameter, inner diameter, and muscle thickness) and 4 for functional measurements (displacement, time to relax, passing duration, and time to contract) were assessed. To verify the pathophysiology of postoperative dysphagia, we examined the change in the ratios of US parameters (=US parameter2 weeks postoperatively/US parameterat baseline) and the existence of significant correlations with change in the EAT-10 score (=EAT-102 weeks postoperatively−EAT-10at baseline). To identify the predictive features, the baseline US parameters were compared between dysphagia (+) and dysphagia (−) groups.

Results:

A total of 46 patients (mean age, 61.3 y; 78.3% male) were included for analysis. A greater increase of the EAT-10 score after surgery was positively correlated with change ratios of the muscle thickness and time to contract and negatively with change ratio of the inner diameter. The dysphagia (+) group exhibited significantly greater inner diameter and smaller muscle thickness at baseline than the dysphagia (−) group.

Conclusion:

Dysphagia during the acute postoperative phase of anterior cervical surgery is caused by the physical narrowing of the inner lumen due to muscle thickening of the UES and sphincter contractile dysfunction. In addition, a baseline UES morphology characterized by a greater inner diameter and a thinner muscle layer is predictive of postoperative dysphagia.
Geospatial Evaluation of Disparities in Access to Cervical Spine Fusion in Metropolitan Areas Across the United States
Authors: Peterman Nicholas , Shivdasani Krishin , Naik Anant , Dharnipragada Rajiv , Harrop James , Vaccaro Alexander R. , Arnold Paul M.
Published: December 2023

Study Design:

Retrospective study with epidemiologic analysis of public Medicare data.

Objective:

The purpose of this study is to use geospatial analysis to identify disparities in access to cervical spine fusions in metropolitan Medicare populations.

Summary of Background Data:

Cervical spine fusion is among the most common elective procedures performed by spine surgeons and is the most common surgical intervention for degenerative cervical spine disease. Although some studies have examined demographic and socioeconomic trends in cervical spine fusion, few have attempted to identify where disparities exist and quantify them at a community level.

Methods:

Center for Medicare and Medicaid Services physician billing and Medicare demographic data sets from 2013 to 2020 were filtered to contain only cervical spine fusion procedures and then combined with US Census socioeconomic data. The Moran Index geospatial clustering algorithm was used to identify statistically significant hotspot and coldspots of cervical spine fusions per 100,000 Medicare members at a county level. Univariate and multivariate analysis was subsequently conducted to identify demographic and socioeconomic factors that are associated with access to care.

Results:

A total of 285,405 cervical spine fusions were analyzed. Hotspots of cervical spine fusion were located in the South, while coldspots were throughout the Northern Midwest, the Northeast, South Florida, and West Coast. The percent of Medicare patients that were Black was the largest negative predictor of cervical spine fusions per 100,000 Medicare members (β=−0.13, 95% CI: −0.16, −0.10).

Conclusions:

Barriers to access can have significant impacts on health outcomes, and these impacts can be disproportionately felt by marginalized groups. Accounting for socioeconomic disadvantage and geography, this analysis found the Black race to be a significant negative predictor of access to cervical spine fusions. Future studies are needed to further explore potential socioeconomic barriers that exist in access to specialized surgical care.

Level of Evidence:

Level III—retrospective.
Combining Skin Adhesive Tape with Incisional Negative Pressure Wound Therapy for Gaping Spinal Wound Dehiscence: A Case Report
Authors: Yang Cassie , Ou Yang Youheng
Published: December 2023

The authors present a case report of spinal wound dehiscence successfully treated with a combination of incisional negative pressure wound therapy and skin adhesive tapes. This article discusses the technique, benefits and limitations, and finally provides a proposed mechanism of action.
A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round
Authors: Couderc Sylvain , Gabriel Anthony , Decheiver Sarah , N'Zoué Kanga Sita , Fikanni Amine , Flint Harry , Pihan Franck , Sahar Abdallah , Tifrea Marius , Tifrea Andrea , Marsaud Jean-Philippe , Vandroux David
Published: December 2023

Background:

This study presents the case of a 19-year-old woman who attempted suicide by ingesting 11.25 g of venlafaxine (V). She was admitted to the hospital with severe biventricular dysfunction, progressing to cardiac arrest requiring extracorporeal circulatory life support for 11 days. The pharmacokinetics of venlafaxine during impaired cardiac output and the effect of its active metabolite, the O-desmethylvenlafaxine (ODV), are currently not very well understood.

Methods and Results:

Serum concentrations of V and ODV were monitored twice daily for 3 weeks. The maximum concentrations of venlafaxine and ODV were at 14 hours after ingestion, with 29,180 mcg/L for V and 5399 mcg/L for ODV. Half-lives increased, requiring 2 weeks to eliminate the drug. The left ventricular ejection fraction significantly improved when V + ODV was below 1000 mcg/L and remained altered until the ODV concentrations were lower than 400 mcg/L.

Conclusions:

This report, with complete elimination kinetic of V and ODV in a monodrug intoxication, provides information about the modification of pharmacokinetics in the case of an overdose managed by extracorporeal circulatory life support, the cardiac toxicity of ODV, and the value of the toxic threshold for the active moiety.
Differentiating left ventricular remodelling in aortic stenosis from systemic hypertension and impact of surgical replacement
Authors: Mahmod Masliza , Chan Kenneth , Fernandes Joao F. , Ariga Rina , Raman Betty , Zacur Ernesto , Law Ho-fon Royce , Rigolli Marzia , Francis Jane , Dass Sairia , O’Gallagher Kevin , Myerson Saul , Karamitsos Theodoros , Neubauer Stefan , Lamata Pablo
Published: December 2023

(2)

Background

Left ventricular (LV) hypertrophy occurs in both aortic stenosis (AS) and systemic hypertension (HTN) in response to wall stress. However, differentiation of hypertrophy due to these two aetiologies is lacking, as well as an understanding of the impact of surgical aortic valve replacement (AVR). The aim was to study the 3-dimensional geometric remodelling pattern in severe AS pre– and post-surgical AVR, and to compare with HTN and healthy controls.

Methods

Ninety-one subjects (36 severe AS, 19 HTN and 36 healthy controls) underwent cine cardiac magnetic resonance (CMR). CMR was repeated eight months post-AVR (n=18). Principal component analysis (PCA) was performed on the 3-dimensional meshes reconstructed from 109 CMR myocardial contours of 91 subjects at end-diastole. PCA modes were compared across experimental groups.

Results

A unique AS signature was identified by wall thickness linked to a LV left-right axis shift and a decrease in short axis eccentricity. HTN was uniquely linked to increased septal thickness. Combining these three features had good discriminative ability between AS and HTN (AUC=0.792). The LV left-right axis shift was not reversible post-AVR and was predictive of post-operative LV mass regression (R2=0.339, p=0.014). AVR was associated with a reduction in global LV size and correction of short axis eccentricity.

Conclusions

Unique remodelling signatures can differentiate the aetiology of LV hypertrophy. LV axis shift is characteristic in AS, is not reversible post AVR, predicts mass regression, and is interpreted to be an adaptive mechanism.

Graphical abstract.
Characterizing Spatial Epidemiology in a Heterogeneous Transmission Landscape Using a Novel Spatial Transmission Count Statistic
Authors: Lyu Leke , Veytsel Gabriella Elizabeth , Stott Guppy , Fox Spencer James , Dailey Cody Aaron , Damodaran Lambodhar , Fujimoto Kayo , Brown Pamela , Sealy Roger , Brown Armand , Alabady Magdy , Bahl Justin
Published: December 2023

Abstract Background Viral genomes contain records of geographic movements and cross-scale transmission dynamics. However, the impact of regional heterogeneity, particularly among rural and urban centers, on viral spread and epidemic trajectory has been less explored due to limited data availability. Intensive and widespread efforts to collect and sequence SARS-CoV-2 viral samples have enabled the development of comparative genomic approaches to reconstruct spatial transmission history and understand viral transmission across different scales. Methods We proposed a novel spatial transmission count statistic that efficiently summarizes the geographic transmission patterns imprinted in viral phylogenies. Guided by a time-scaled tree with ancestral trait states, we identified spatial transmission linkages and categorize them as imports, local transmissions, and exports. These linkages were then summarized to represent the epidemic profile of the focal area. Results We demonstrated the utility of this approach for near real-time outbreak analysis using over 12,000 full genomes and linked epidemiological data to investigate the spread of the SARS-CoV-2 in Texas. Our study showed (1) highly populated urban centers were the main sources of the epidemic in Texas; (2) the outbreaks in urban centers were connected to the global epidemic; and (3) outbreaks in urban centers were locally maintained, while epidemics in rural areas were driven by repeated introductions. Conclusions In this study, we introduce the Source Sink Score, which allows us to determine whether a localized outbreak may be the source or sink to other regions, and the Local Import Score, which assesses whether the outbreak has transitioned to local transmission rather than being maintained by continued introductions. These epidemiological statistics provide actionable information for developing public health interventions tailored to the needs of affected areas.
Malaria species prevalence among asymptomatic individuals in four regions of Mainland Tanzania
Authors: Popkin Hall Zachary R. , Seth Misago D. , Madebe Rashid A. , Budodo Rule , Bakari Catherine , Francis Filbert , Pereus Dativa , Giesbrecht David J. , Mandara Celine I. , Mbwambo Daniel , Aaron Sijenunu , Lusasi Abdallah , Lazaro Samwel , Bailey Jeffrey A. , Juliano Jonathan J. , Gutman Julie R. , Ishengoma Deus S.
Published: December 2023

Recent studies point to the need to incorporate non-falciparum species detection into malaria surveillance activities in sub-Saharan Africa, where 95% of malaria cases occur. AlthoughPlasmodium falciparuminfection is typically more severe, diagnosis, treatment, and control forP. malariae,P. ovalespp., andP. vivaxmay be more challenging. The prevalence of these species throughout sub-Saharan Africa is poorly defined. Tanzania has geographically heterogeneous transmission levels but an overall high malaria burden. In order to estimate the prevalence of malaria species in Mainland Tanzania, 1,428 samples were randomly selected from 6,005 asymptomatic isolates collected in cross-sectional community surveys across four regions and analyzed via qPCR to detect eachPlasmodiumspecies.P. falciparumwas most prevalent, withP. malariaeandP. ovalespp. detected at lower prevalence (<5%) in all four regions.P. vivaxwas not detected. Malaria elimination efforts in Tanzania will need to account for these non-falciparum species.
Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment
Authors: Shook Lydia L. , Batorsky Rebecca A. , De Guzman Rose M. , McCrea Liam T. , Brigida Sara M. , Horng Joy E. , Sheridan Steven D. , Kholod Olha , Cook Aidan M. , Li Jonathan Z. , Goods Brittany A. , Perlis Roy H. , Edlow Andrea G.
Published: December 2023

The SARS-CoV-2 virus activates maternal and placental immune responses, which in the setting of other infections occurring during pregnancy are known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluatein uteromicroglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. Here, we assessed the impact of maternal SARS-CoV-2 on HBCs isolated from term placentas using single-cell RNA-sequencing. We demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells, with altered morphology and impaired synaptic pruning behavior compared to HBC models from negative controls. These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.
Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment
Authors: Ugalde-Triviño Lola , Molina-Jiménez Francisca , H-Vázquez Juan , Relaño-Rupérez Carlos , Arias-González Laura , Casabona Sergio , Pérez-Fernández María Teresa , Martín-Domínguez Verónica , Fernández-Pacheco Jennifer , Lucendo Alfredo J , Bernardo David , Santander Cecilio , Majano Pedro
Published: December 2023

Objectives

The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response.

Methods

PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis of immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients.

Results

Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI.

Conclusions

We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

WHAT IS KNOWN

Eosinophilic esophagitis (EoE) is a Th2 type immune disorder with increased prevalence in the last years.

Proton pump inhibitor (PPI) treatment is the preferred first-line therapy for EoE, which leads to clinical and pathological reversion in about half of the cases. Non-responding patients require other therapeutic options.

Currently, an endoscopy with esophageal biopsies is required for EoE diagnosis and to monitor response to treatment. Therefore, the discovery of non-invasive biomarkers is of utmost importance for treatment monitoring.

To date only peripheral eosinophil and Th2 profiles have been studied in EoE.

WHAT IS NEW HERE

At diagnosis EoE patients have a specific circulating immune signature.

PPI-responding and non-responding EoE patients have different immune fingerprints at baseline.

Immune characterization of EoE patients at diagnosis and after PPI treatment unveiled differential levels of circulating plasmacytoid dendritic cells (pDCs) depending on their inflammatory state and response to PPI treatment. Those levels are related with the number of pDCs infiltrated in the esophageal tissue.
Systematic Review of Prevalence of Sleep Problems in India: A Wake- up Call for Promotion of Sleep Health
Authors: Datta Karuna , Bhutambare Anna , Mallick Hruda Nanda
Published: December 2023

An ever-increasing burden of non-communicable diseases, especially in the post pandemic times and an association of sleep problems with them highlighted a felt need to estimate the sleep problem in India. A meta-analysis of the studies conducted on Indian data was planned adhering to PRISMA guidelines. An electronic search of available literature was performed on databases including PubMed, Google Scholar, PsycNet, and Epistemonikos. 100 eligible articles were analysed. To assess the methodological quality 10-points Joanna Briggs Institute (JBI) checklist for prevalence studies was used. The pooled estimates for prevalence of Insomnia found were 25.7%, OSA 37.4%, and RLS 10.6%. An increased prevalence was seen in patients of diabetes, heart disease patients and in otherwise healthy population. Subgroup analysis showed a higher prevalence in patient population and in the otherwise healthy population too,; e.g. Insomnia 32.3% (95% CI: 18.6% to 49.9%, I2=99.4%) and 15.1% (95% CI: 8.0% to 26.6%, I2=99.1%); OSA 48.1% (95% CI: 36.1% to 60.3%, I2=97.4%) and 14.6% (95% CI: 9.2% to 22.5%, I2=97.4%) and RLS 13.1% (95% CI: 8.7% to 19.3%, I2=91.9%) and 6.6% (95% CI: 2.4% to 16.4%, I2=99.1%) respectively. Excessive daytime sleepiness remained prevalent (19.6%) (95 % CI: 8.4% to 39.1%, I2=99.8%) in the healthy, which was alarming. A multipronged approach for sleep management, evaluation and research is the need of the hour for managing non communicable disorders and for promoting sleep health in the healthy population.
Assessing the effectiveness of near real-time flow cytometry in monitoring ozone disinfection in a full-scale drinking water treatment plant
Authors: Dowdell Katherine S. , Olsen Kirk , Martinez Paz Ernesto F. , Sun Aini , Keown Jeff , Lahr Rebecca , Steglitz Brian , Busch Andrea , LiPuma John J. , Olson Terese , Raskin Lutgarde
Published: December 2023

While real-time monitoring of physicochemical parameters has widely been incorporated into drinking water treatment systems, real-time microbial monitoring has lagged behind, resulting in the use of surrogate parameters (disinfectant residual, applied dose, concentration × time [CT]) to assess disinfection system performance. Near real-time flow cytometry (NRT-FCM) allows for automated quantification of total and intact microbial cells but has not been widely implemented in full-scale systems. This study sought to investigate the feasibility of NRT-FCM for full-scale drinking water ozone disinfection system performance monitoring. A water treatment plant with high lime solids turbidity in the ozone contactor influent was selected to evaluate the NRT-FCM in challenging conditions. Total and intact cell counts were monitored for 40 days and compared to surrogate parameters (ozone residual, ozone dose, and CT) and grab sample assay results for cellular adenosine triphosphate (cATP), heterotrophic plate counts (HPC), impedance flow cytometry, and 16S rRNA gene sequencing. NRT-FCM provided insight into the dynamics of the full-scale ozone system, including offering early warning of increased contactor effluent cell concentrations, which was not observed using surrogate measures. A strong correlation between log intact cell removal and CT was also not observed (Kendall’s tau= −0.09, p=0.04). Positive correlations were observed between intact cell counts and cATP levels (Kendall’s tau=0.40, p<0.01), HPC (Kendall’s tau=0.20, p<0.01), and impedance flow cytometry results (Kendall’s tau=0.30, p<0.01). However, 16S rRNA gene sequencing results showed that passage through the ozone contactor significantly changed the microbial community (p<0.05), supporting the hypothesis that regrowth was occurring in the later chambers of the contactor. This study demonstrates the utility of direct, near real-time microbial analysis for monitoring full-scale disinfection systems.

Graphical Abstract

Highlights

Near real-time flow cytometry (NRT-FCM) was effective for ozone system monitoring.

Intact microbial cell counts were consistent with cellular ATP and HPC results.

NRT-FCM provided early detection of increased effluent cell concentrations.

The ozone contactor influent and effluent microbial communities were distinct.
Node Features of Chromosome Structure Network and Their Connections to Genome Annotation
Authors: Xu Yingjie , Das Priyojit , McCord Rachel P. , Shen Tongye
Published: December 2023

The 3D conformations of chromosomes can encode biological significance, and its implication is being increasingly appreciated recently. Certain chromosome structural features, such as A/B compartmentalization, are frequently extracted from pairwise contact information (physical association between different regions of the genome) and compared with linear annotations of the genome, such as histone modifications and lamina association. Here, we investigate how additional properties of chromosome structure can be deduced using the abstract graph representation of the contact heatmap, and how network properties can have a better connection with some of these biological annotations. We constructed chromosome structure networks (CSNs) from bulk Hi-C data and calculated a set of site-resolved (node-based) network properties of these CSNs. We found these network properties are useful for characterizing chromosome structure features. We examined the ability of network properties in differentiating several scenarios, such as haploid vs diploid cells, partially inverted nuclei vs conventional architecture, and structural changes during cell development. We also examined the connection between network properties and a series of other linear annotations, such as histone modifications and chromatin states including poised promoter and enhancer labels. We found that semi-local network properties are more capable of characterizing genome annotations than diffusive or ultra-local node features. For example, local square clustering coefficient can be a strong classifier of lamina-associated domains (LADs), whereas a path-based network property, closeness centrality, does not vary concordantly with LAD status. We demonstrated that network properties can be useful for discerning large-scale chromosome structures that emerge in different biological situations.

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