bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical methods for filamentous fungi
Authors: Döhren Hans von
Published: November 2023

Although biochemical approaches in the study of filamentous fungi may be considered more complex than bacterial or yeast studies, this is not obvious from current protocols. Fairly little attention has so far been given to morphological specialities (except for mycelium and spore structures) and ultrastructural compartmentation. This will hopefully improve in the future with rising interest in cell biological questions. Biochemistry of fungi includes the description of constituents, and here focus is given to proteins and metabolites. At this time, the genomes of filamentous fungi have not been fully sequenced, and/or no genome sequence is as yet available in the public domain. Still, proteomics is entering the field, and will be involved in problem solution in the near future.
Lymphocyte culture
Authors: Clouston H J
Published: November 2023

Cytogenetic analysis of blood samples is the largest concern of most constitutional cytogenetics laboratories. There are two main reasons why peripheral blood remains the tissue of choice for postnatal studies. First, blood samples are comparatively easy to obtain. Second, simple, relatively inexpensive culture techniques can be used to rapidly generate abundant metaphases of optimum length and quality. These preparations are ideal for high-resolution G-banding and FISH studies.

This chapter describes the techniques and rationale of lymphocyte culture and chromosome preparation, and includes protocols with which the author has achieved considerable success.
The application of cytogenetic investigations to clinical practice
Authors: Wolstenholme J , Burn J
Published: November 2023

Cytogenetic investigations are expensive. It is inappropriate to perform cytogenetic screening on unselected populations or to apply all the available culture and staining techniques to every sample. This is particularly so for the explosion of FISH-based approaches which are currently moving from the research environment to the diagnostic laboratory. At present, many are prohibitively expensive, extremely time-consuming and require specialized equipment for analysis. Their place in mainstream diagnostic laboratories is thus restricted to certain referral categories, but based on previous experience, this may change rapidly as these drawbacks are overcome.
Fluorescent probes for living plant cells
Authors: Fricker Mark , Parsons, Andrew , Tlalka Monika
Published: November 2023

There are several reviews that cover the biological questions that have been addressed with fluorescent techniques in plants (1-3) and there is extensive on line documentation on the properties of the fluorescent probes themselves (e.g. Molecular Probes, . This chapter focuses on optimization of the systems used for live cell imaging, the methods used to mount plant specimens and load them with dyes, a compendium of dyes that have proved useful in plant tissues, and a series of protocols to convert qualitative observations to quantitative measurements. The hazards associated with these dyes are, in the main, not known, so all should be treated as potentially harmful.
Flow cytometry
Authors: Pena Teodoro Coba de la , Brown Spencer
Published: November 2023

Single cell biochemistry, single cell screening, and assessment of heterogeneity in cell populations have become feasible in both fundamental and industrial situations. These strategies have benefited from the following happy marriage. On one hand we have development of thousands of fluorescent markers for probing cellular functions, physiological states, or gene expression (Chapters 2, 4, 5), to which one must add the diagnostic tools of in situ hybridization (Chapter 12) and immunolabelling (Chapters 10, 11). On the other hand we have the numerical power, simplicity, and sensitivity of cytometry. This term conveys cell-by-cell quantification of structure or, typically, of fluorescent signals. This may be achieved by quantitative microscopy-or by flow cytometry, in which case no image is obtained but fluorescent intensities are measured with remarkable ease and precision. There is not space to handle cell physiological studies here, although vacuolar properties (1), pH (2), relative membrane potential (3), and membrane viscosity (4) can be assessed by cytometry.
Chaperones in secretion pathl’Vays of E. coli
Authors: Harms Nellie , Luirink Joen , Oudega Bauke
Published: November 2023

Cytoplasmic proteins once synthesized at the ribosome fold into their native conformation, whereas proteins with destinations outside the cytoplasm are targeted to the cytoplasmic membrane and have to be prevented from premature folding and from degradation. For the majority of these latter proteins, folding occurs outside the cytoplasm. The precision and speed of these processes is ensured by different chaperones, targeting factors and folding catalysts. Most of these helper proteins, present in the cytoplasm, the periplasm, and in the membranes have a general role; some, however, are dedicated to special processes. This review focuses on the targeting and folding processes that function in a number of secretion pathways of E. coli. Since the field of protein secretion is very broad, not all pathways and their concomitant chaperones will be described.
Regulation of expression of molecular chaperones
Authors: Lund Peter A
Published: November 2023

Many molecular chaperones are also heat shock proteins: their expression in cells is elevated when the cells are exposed to temperatures a few degrees above normal growth temperature. The regulation of the heat shock response has been the subject of intense study for some years, partly because, as with all expression studies, there is considerable interest in tracing the pathways that lead from an external effect (in this case, an increase in temperature) which generates some kind of inducing signal that can be read by components in the cell, through to a change in gene expression. Following the pathways from external signal to gene induction becomes particularly intriguing when the signal is read in a cellular compartment which is separated by one or more membranes from where the response takes place. As many heat shock proteins are also molecular chaperones, there is also considerable interest in relating the nature of the inducing signal(s) to the processes with which the chaperones are involved. In this chapter, I will discuss some of the many ways in which organisms can sense the need for elevated chaperone expression, predominantly by using examples drawn from prokaryotes where many of these pathways have been well characterized. I will endeavour in several cases to follow the pathways from the external event to the change in gene expression, and to discuss the experimental evidence for the nature of the intracellular inducing signals. Some aspects of the regulation of chaperone gene expression by stress in eukaryotes will also be briefly discussed in the same light.
Protease-based selection of stably folded proteins and protein domains from phage display libraries
Authors: Tuna Mihriban , Finucane Michael D , Vlachakis Natalie G M , Woolfson Derek N
Published: November 2023

Until recently, selection from phage display libraries has relied on binding of the displayed proteins to targeted ligands. While a wide variety of targets from small molecules to nucleic acids and proteins have been employed, these traditional bio-panning methods limit potential applications of phage display technology. Here we describe methods for selecting proteins from libraries based on their stability/structural integrity alone. This may be desirable in cases where no selectable protein function is available, for example in de novo design or proteomics. Three groups have presented different solutions to this problem: those of Plu.ckthun/Schmid (1), Winter (2) and our own group (3). We will focus on our own studies with the aim of teaching how to select stably folded proteins from a variety of phage display libraries.
Interaction cloning using cDNA libraries displayed on phage
Authors: Jespers Laurent , Fransen Marc
Published: November 2023

Expression cloning of complementary DNA (cDNA) is an extremely valuable tool for the isolation and characterization of genes. Whereas nucleic acid probe-based screening relies on preliminary sequence information related to the gene of interest, screening of an expressed cDNA library only requires a natural ligand or a specific (monoclonal or polyclonal) antibody as probe (1, 2). In vitro screening of cDNA libraries expressed from A phage or plasmids involves affixing the translated products to a membrane prior to challenging with a labeled probe. This transfer can denature the cDNA-encoded proteins and may therefore com- promise detection. In contrast, the yeast-based two-hybrid system operates entirely in vivo by reconstituting a transcriptional activator to detect protein-- protein interactions via the expression of a reporter gene (3). Overall, these systems are not easily amenable to the screening of large libraries and this has triggered the development of several systems based on selection rather than screening. In view of sensitivity and selectivity, selection for a specific interaction through iterative enrichment steps is less demanding than screening. However, cDNA cloning via selection of expressed clones requires a physical linkage between each cDNA (for propagation) and its gene product (for detec- tion). One of the first selection systems designed for expression cloning of cDNA was developed for isolation of mammalian cell transformants expressing specific cell receptors (4). Recently, the advent of phage display technology (for reviews, see 5-6) as a powerful tool for selection of specific binding peptides or proteins from large libraries (210 clones) has provided the opportunity to develop this system for expression cloning of cDNA.
Comparative genomic hybridization on metaphase chromosomes and DNA chips
Authors: Joos Stefan , änen Carsten Schw , Lichter Peter
Published: November 2023

Comparative genomic hybridization (CGH) allows a genome-wide screening of chromosomal imbalances without prior knowledge of genomic regions of interest and independent of the availability of metaphase cells from the specimens to be investigated. Since its first description (1) CGH became a powerful alternative to chromosome, banding and fluorescence in situ hybridization (FISH) analyses (2-4) and has contributed significantly to the current knowledge of genomic alterations in a large number of tumour entities (for an overview see refs 5 and 6).
America
Authors: Hamilton W D
Published: November 2023

The paper of this chapter was my first intellectual wild oat, the first for publication in a symposium volume. Others were to follow and my promiscuity of the kind has increased steadily. The oats are incited by such temptations as reputation, money (honoraria), and travel to exciting places. Defects of the present example will prepare the reader for the regular shortcomings which are haste, lack of focus, and lack of anything new to say.
Panic Stations
Authors: Hamilton W D
Published: November 2023

This was a theme that I had worked out in note form long before I tried to publish it. Once again the idea began in an irritation while I was still an undergraduate reading and hearing about schooling, flocking, and herding habits of animals. My doubts that these phenomena were being correctly interpreted became more focused when V. C. Wynne-Edwards of the University of Aberdeen published in 1962 his book Animal Dispersion in Relation to Social Behaviour, which suggested that a population display and self-census function was involved in many instances of aggregation. He unhesitatingly appealed to selection at the population level to explain how such phenomena had arrived. I could not see that this view was either necessary or likely.
Advanced Arts of Exit
Authors: Hamilton W D
Published: November 2023

Hugh Comins came to Imperial College Field Station in May 1974. Like Robert May he was Australian and had a doctorate in theoretical physics. Like May he came a viking into the quiet hall of Silwood, brandishing an analytical skill against which we entomologists and ecologists had no defence. Vikings, extraterrestrials, Ned Kellys blazing against Authority and the Old Country—our only hope was to get them on our side. Our pacification efforts seem to have worked reasonably well as, I think, Chapter 11, the paper discussed here, and many others coming out of Silwood around that time attest.
Hypoxia‐sensing VGLL4 promotes LDHA‐driven lactate production to ameliorate neuronal dysfunction in a cellular model relevant to Alzheimer's disease
Authors: Tian Qiuyun , Li Junjie , Wu Bin , Wang Jiaojiao , Xiao Qian , Tian Na , Yi Lilin , Luo Man , Li Zhaolun , Pang Yayan , Shi Xiuyu , Dong Zhifang
Published: November 2023

Alzheimer's disease (AD) is a neurodegenerative disease where abnormal amyloidogenic processing of amyloid‐β precursor protein (APP) occurs and has been linked to neuronal dysfunction. Hypometabolism of glucose in the brain can lead to synaptic loss and neuronal death, which in turn exacerbates energy deficiency and amyloid‐β peptide (Aβ) accumulation. Lactate produced by anaerobic glycolysis serves as an energy substrate supporting neuronal function and facilitating neuronal repair. Vestigial‐like family member 4 (VGLL4) has been recognized as a key regulator of the hypoxia‐sensing pathway. However, the role of VGLL4 in AD remains unexplored. Here, we reported that the expression of VGLL4 protein was significantly decreased in the brain tissue of AD model mice and AD model cells. We further found that overexpression of VGLL4 reduced APP amyloidogenic processing and ameliorated neuronal synaptic damage. Notably, we identified a compromised hypoxia‐sensitive capability of LDHA regulated by VGLL4 in the context of AD. Upregulation of VGLL4 increased the response of LDHA to hypoxia and enhanced the expression levels of LDHA and lactate by inhibiting the ubiquitination and degradation of LDHA. Furthermore, the inhibition of lactate production by using sodium oxamate, an inhibitor of LDHA, suppressed the neuroprotective function of VGLL4 by increasing APP amyloidogenic processing. Taken together, our findings demonstrate that VGLL4 exerts a neuroprotective effect by upregulating LDHA expression and consequently promoting lactate production. Thus, this study suggests that VGLL4 may be a novel player involved in molecular mechanisms relevant for ameliorating neurodegeneration.
Group B Streptococcal Disease in Infants in Japan
Authors: Matsubara Kousaku , Shibata Meiwa
Published: November 2023

This review describes the epidemiology of group B Streptococcus (GBS) infection in infants in Japan and discusses unresolved issues and future perspectives. Guidelines for the prevention of vertical transmission in Japan were implemented in 2008. The incidence of early-onset disease in Japan has remained stable at approximately 0.10/1000 livebirths or less, which is lower than in Europe and North America. The incidence of late-onset disease is also low, but has increased over the last decade, with an estimated 0.29/1000 livebirths in 2020. National surveillance studies in 2011–2015 and 2016–2020 reported case fatality rates of 4.5% and 6.5% for early-onset disease and 4.4% and 3.0% for late-onset disease, respectively. Sequelae of neurodevelopmental impairments were considerably associated with infants who developed meningitis. Predominant neonatal invasive strains have remained in the following order of serotypes: III, Ia, Ib and V, for the past 30 years. Conversely, the predominant serotypes of maternal colonization strains markedly changed from serotypes VI and VIII around 2000 to serotypes Ia, Ib, III and V over the last decade. Recurrence rates among infants < 1-year-old were estimated to be 2.8%–3.7%, and preterm birth and antenatal maternal GBS colonization were risk factors for recurrence. Several unresolved issues remain. First, the exact disease burden remains unclear because Japan does not have a nationwide system to register all infants affected by invasive GBS disease, and even population-based surveys are limited to up to 10 of the 47 prefectures. Others include low adherence to prevention guidelines of vertical transmission and the development of strategies based on Japanese epidemiological evidence rather than the Center for Disease Control and Prevention guidelines. The effectiveness of introducing maternal vaccines in Japan, where the disease incidence is low, needs to be carefully verified.
Interventions to Reduce Inappropriate Physical Therapy Consultation in the Inpatient Setting: A Quality Improvement Initiative
Authors: Patel Moksha , Gardner Tiffany A. , White Christopher , Keniston Angela , Maassen Becky , Gottenborg Emily
Published: November 2023

Physical therapy (PT) in inpatient settings is a limited and valuable resource. Inappropriate PT consultation is costly and can lead to delays in care and discharge planning. Baseline data at an academic hospital revealed that approximately one in four PT consults were inappropriate (n = 29,230) across all services, as defined by an activity measure post–acute care “6-Clicks” basic mobility score of >22. Our interdisciplinary quality improvement team used the Six Sigma methodology to address this problem. We performed a root-cause analysis that identified high-impact root causes and implemented two targeted interventions: (1) A modified electronic health record PT order with clinical-decision support, and (2) nursing role change to assume PT-ordering responsibility. The rate of inappropriate PT consults decreased from 23.9% to <10% postintervention across all inpatient units, with the nursing role change reaching statistical significance (p < .0019). Our multifaceted intervention contributed to a significant reduction in unnecessary PT consults, expediting evaluation of patients qualifying for skilled inpatient therapy.
Postoperative Oral Care Pathways Are Not Required at the Time of Buccal Mucosa Harvest
Authors: Krughoff Kevin , Foreman Jordan , Dvergsten Thomas , Peterson Andrew C.
Published: November 2023

Purpose:

For patients undergoing urethroplasty with buccal mucosa grafting, the impact of oral care pathways on infection and pain control remains unstudied. We hypothesize that the elimination of dietary restrictions and mouthwash regimens from the oral care pathway would not alter the rate of donor site complications.

Materials and Methods:

One hundred urethroplasty cases using buccal mucosa were retrospectively reviewed for donor site and perineal wound complications. No preoperative or intraoperative antibiotic oral cleanses were used in any case. Records were categorized by use of postoperative dietary restrictions and mouthwash regimens. Graft harvest size, preexisting oral issues, baseline comorbidities, dental assessments, perioperative antibiotics, and postoperative pain control regimens were accounted for.

Results:

Forty patients were included in the oral care pathway and 60 in the nonoral care pathway. Baseline demographics, dental assessment, and graft harvest details were similar between groups. There were no cases of graft site infection, with a median follow-up of 226 days. All graft site issues resolved in 3 to 4 weeks or less. Perineal wound infections for oral care pathway 2 (5%), and no oral care pathway 4 (6.7%), P = .6. Urinary tract infections for oral care pathway 7 (17.5%), and no oral care pathway 2 (3.3%), P = .027.

Conclusions:

Postoperative oral complications remain low without the use of oral cleanses, dietary restrictions, or mouthwash regimens. Routine use of donor site care pathways is likely unnecessary in this patient population.
Improving effective depression care in an outpatient psychiatric clinic
Authors: Moore Thomas , Johnson Sharanna
Published: November 2023

Background:

With more than 20 million adults experiencing a major depressive episode in 2020, depression is one of the most widespread and costly illnesses in the United States.

Local problem:

An audit of medical records at an outpatient psychiatric clinic revealed that none of the patients (0/56) were receiving standardized depression screening at follow-up appointments.

Methods:

An 8-week rapid cycle Plan-Do-Study-Act model for change was used to spearhead a quality improvement (QI) project for effective depression care. The QI project comprised ongoing data collection through chart audit every 3 days, which drove tests of change (TOC). Team engagement surveys were also assessed for change in team engagement scores.

Interventions:

The Patient Health Questionnaire-9 (PHQ-9) was used to assess depression, and an effective care log (ECL) measured effective depression care. Every 2 weeks, a TOC was implemented, which guided further iterative changes throughout the project.

Results:

Effective depression care increased to 74% over the course of the project, surpassing the initial aim of 50%. Completion rates of the PHQ-9 (76%) and ECL (91%) increased. Team engagement (27.1) also increased over the course of the project.

Conclusions:

This project improved effective depression care. The success was largely due to the iterative TOCs, ECL, and team engagement.
Survivors' Experiences of Hyperemesis Gravidarum
Authors: Beck Cheryl Tatano
Published: November 2023

Hyperemesis gravidarum can result in life-threatening physical and psychological maternal morbidity, including severe dehydration, weight loss, electrolyte imbalance, depression, and suicidal ideation. The reported prevalence of hyperemesis gravidarum ranges from 0.3% to 3.6%. The purpose of this qualitative study was to investigate what blogs can tell us about women's experiences of hyperemesis gravidarum. Thirty-three blogs written by hyperemesis gravidarum survivors posted on Hyperemesis Australia's website were analyzed using Krippendorff's qualitative content analysis method. Clustering was used and yielded 6 themes: (1) debilitating physical and mental health problems: digging deep to persevere, (2) heartbreaking choices, (3) lack of understanding and dismissed, (4) so much guilt surrounding their unborn infant, (5) it takes a village to support women with hyperemesis gravidarum, and (6) warriors and survivors: giving back. Infusion nurses are in a perfect position to provide support and compassionate care for women who are repeatedly coming to the hospital for rehydration treatment. Infusion nurses can validate women's physical and emotional struggles with hyperemesis gravidarum and help to no longer make women feel stigmatized.
The Relationship Between Melatonin 1-2 Receptor Expression in Patients With Epithelial Ovarian Cancer and Survival
Authors: Bicer Elifnur , Bese Tugan , Tuzun Deniz Dilan , Ilvan Sennur , Kayan Basak Ozge , Demirkiran Fuat
Published: November 2023

Melatonin has antiproliferative, antiangiogenic, apoptotic, and immunomodulatory properties in ovarian cancer. Considering those, we evaluated the relationship between melatonin 1 (MT1) and melatonin 2 receptor (MT2) expression in tumor tissues of patients with epithelial ovarian cancer, disease-free survival (DFS), and overall survival (OS). Patients who received primary surgical treatment for epithelial ovarian cancer in our clinic between 2000 and 2019 were retrospectively scanned through patient files, electronic databases, and telephone calls. One hundred forty-two eligible patients were included in the study, their tumoral tissues were examined to determine MT1 and MT2 expression by immunohistochemical methods. The percentage of receptor-positive cells and intensity of staining were determined. MT1 receptor expression (P = 0.002 for DFS and P = 0.002 for OS) showed a significant effect on DFS and OS. MT2 expression had no effect on survival (P = 0.593 for DFS and P = 0.209 for OS). The results showed that the higher the MT1 receptor expression, the longer the DFS and OS. It is suggested that melatonin should be considered as adjuvant therapy for ovarian cancer patients in addition to standard treatment, and clinical progress should be observed.
Diagnostic Challenges and Long-term Outcomes of Neuroendocrine Carcinoma of the Cervix: A Case Series
Authors: Lamiman Kelly , Wilhelm Alyeesha B. , Eyzaguirre Eduardo , Richardson Gwyn
Published: November 2023

Neuroendocrine carcinomas (NECs) of the cervix are rare, aggressive malignancies that are challenging to diagnose and treat. They are high-grade lesions that often share features with poorly differentiated adenocarcinoma and squamous cell carcinoma. NECs are classified into large-cell or small-cell subtypes but can often have a mixed appearance or occur concurrently with a squamous or adenocarcinoma. Diagnosis is dependent on tissue sampling, histomorphology, and immunohistochemistry. Eight cases of NEC were retrieved from the Department of Pathology at our institution from 2008 to 2022. Tumor slides were reviewed and evaluated by 2 independent pathologists. Seven of 8 patients tested positive for neuroendocrine markers, including CD56, synaptophysin, and chromogranin. We discuss the diagnostic challenges, review the histopathology, and describe the treatment courses and clinical outcomes. This case series reveals that traditional markers, such as p16, p63, and p40, may be focally positive in NEC and should not be considered a confirmation of squamous cell carcinoma. Patient outcomes can be affected by delays in diagnosis, misdiagnosis, and inadequate treatment when NEC is not considered in the initial differential diagnosis.
Divergent Malignant Melanocytic Differentiation in Ovarian Endometrioid Adenocarcinoma With Aberrant β-Catenin Expression: A Case Expanding the Histologic Spectrum of β-Catenin Activated Gynecologic Neoplasia
Authors: Xu Jin , Weisman Paul S.
Published: November 2023

Divergent differentiation in gynecologic carcinomas encompasses a broad range of lineages, including mesenchymal, germ cell, high-grade neuroendocrine, neuroectodermal, and cutaneous adnexal differentiation. Here we present a case of ovarian endometrioid adenocarcinoma with divergent malignant melanocytic differentiation (MMeD). The background ovarian endometrioid adenocarcinoma showed focally aberrant β-catenin expression and histologic patterns associated with β-catenin activation, including spindled elements and corded and hyalinized foci. The areas with MMeD had both spindled and epithelioid morphology, diffusely aberrant β-catenin expression, expression of melanocytic markers (an HMB45/Mart-1 cocktail, MITF, and S100), and no staining for myogenic markers (SMA and desmin) or epithelial markers (cytokeratins and E-cadherin). INI1, BRG1, PMS2, and MSH6 were retained, and p53 showed a wild-type expression pattern. No areas with definitive carcinosarcomatous differentiation were identified despite extensive sampling. While a single case of gynecologic carcinosarcoma with a serous epithelial component and a small focus on malignant melanoma has been reported in the English literature, the current case represents what is, to the best of our knowledge, the first case of MMeD arising in the context of a β-catenin activated endometrioid adenocarcinoma. Pathogenetic and differential diagnostic considerations are discussed.
Lessons learned in translating pain knowledge into practice
Authors: Becker Juliane , Effraim Philip R. , Dib-Hajj Sulayman , Rittner Heike L.
Published: November 2023

Introduction:

During the past 2 decades, basic research deciphering the underlying mechanisms of nociception and chronic pain was thought to finally step beyond opioids and nonsteroidals and provide patients with new analgesics. But apart from calcitonin gene–related peptide antagonists, nothing arrived in hands of clinicians.

Objectives:

To present existing evidence of 3 representative target molecules in the development of novel pain treatment that, so far, did not result in approved drugs.

Methods:

This Clinical Update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews best available evidence and practice.

Results:

We highlight 3 targets: a ion channel, a neuronal growth factor, and a neuropeptide to explore why these drug targets have been dropped in clinical phase II–III trials. Antibodies to nerve growth factor had very good effects in musculoskeletal pain but resulted into more patients requiring joint replacements. Blockers of NaV1.7 were often not effective enough—at least if patients were not stratified. Blockers of neurokinin receptor were similarly not successful enough. In general, failure was most often to the result of a lack of effect and to a lesser extend because of unexpected severe side effects. However, all studies and trials lead to an enormous move in the scientific community to better preclinical models and testing as well as revised methods to molecularly phenotype and stratify patients.

Conclusion:

All stakeholders in the process can help in the future: better preclinical studies, phenotyping and stratifying patients, and participation in clinical trials to move the discovery of analgesics forward.
The role of micro-RNAs in neuropathic pain—a scoping review
Authors: Kovanur Sampath Kesava , Belcher Suzie , Hales James , Thomson Oliver P. , Farrell Gerard , Gisselman Angela Spontelli , Katare Rajesh , Tumilty Steve
Published: November 2023

Neuropathic pain can be caused by a lesion or disease of the somatosensory system characterised by pathological neuro-immune alterations. At a molecular level, microRNAs (miRNAs) act as regulators of gene expression orchestrating both immune and neuronal processes. Thus, miRNAs may act as essential modulators of processes for the establishment and maintenance of neuropathic pain. The objective/aims of this scoping review was to explore and chart the literature to identify miRNAs that are dysregulated in neuropathic pain. The following databases were searched from inception to March 2023: PubMed, EBSCO, CINAHL, Cochrane Library, and SCOPUS. Two independent reviewers screened, extracted data, and independently assessed the risk of bias in included studies. The JBI critical appraisal checklist was used for critical appraisal. A narrative synthesis was used to summarise the evidence. Seven studies (total of 384 participants) that met our eligibility criteria were included in this scoping review. Our review has identified different miRNAs that are commonly involved in the chronic neuropathic pain conditions including miR-132, miR-101, and miR-199a. Our review findings further suggest that expression of miRNAs to be significantly associated with increased diabetic disease duration, HbA1C levels, and fibrinogen levels. Our review findings suggest that there is clear association between miRNA expression and chronic neuropathic pain conditions. Therefore, increasing the specificity by selecting a candidate miRNA and identifying its target mRNA is an area of future research.
Cadaveric Feasibility Study on Modified Contralateral C7 Nerve Transfer for Targeted Recovery in Hemiplegic Arms
Authors: Zhu Shuai , Ye Xuan , Feng Jun-Tao , Li Tie , Yin Hua-Wei , Qiu Yan-Qun , Xu Wen-Dong , Shen Yun-Dong
Published: November 2023

Background:

Contralateral cervical seventh (cC7) nerve to C7 transfer has been proven effective for treating spastic upper limb. However, for those whose major impairment is not in the C7 area, cC7 nerve transfer to other nerves may achieve a better outcome. The aim of this study was to explore the optimal surgical approach for transferring cC7 to 1 or 2 nerves in a cadaveric study, and to evaluate possible applications for patients with hemiplegia.

Methods:

Modified cC7 transfer to 1 (5 procedures) or 2 nonadjacent (3 procedures) nerve roots was proposed, and success rates of direct coaptation through 2 surgical approaches—the superficial surface of longus colli (sLC) and the deep surface of longus colli (dLC) approach—were compared. The length, diameter, and distance of relevant nerves were also measured in 25 cadavers.

Results:

Compared with the sLC approach, the distance of the dLC approach was 1.1 ± 0.3 cm shorter. The success rates for the sLC and dLC approaches were as follows: cC7 to C5 surgery, 94%, and reached 98%; cC7 to C6 surgery, 54% and 96%; cC7 to C7 surgery, 42% and 94%; cC7 to C8 surgery, 34% and 94%; cC7 to T1 surgery, 24% and 62%; cC7 to C5C7 surgery, 74% and 98%; cC7 to C6C8 surgery, 54% and 98%; and cC7 to C7T1 surgery, 42% and 88%.

Conclusions:

The dLC approach greatly improved the direct coaptation rate for cC7 nerve transfer. The modified cC7 nerve transfer procedures are technically feasible for further application in clinic.
Medication Safety Gaps in English Pediatric Inpatient Units: An Exploration Using Work Domain Analysis
Authors: Sutherland Adam , Phipps Denham L. , Gill Andrea , Morris Stephen , Ashcroft Darren M.
Published: November 2023

Objectives

Medication is a common cause of preventable medical harm in pediatric inpatients. This study aimed to examine the sociotechnical system surrounding pediatric medicines management, to identify potential gaps in this system and how these might contribute to adverse drug events (ADEs).

Methods

An exploratory prospective qualitative study in pediatric wards in three hospitals in the north of England was conducted between October 2020 and May 2022. Analysis included a documentary analysis of 72 policies and procedures and analysis of field notes from 60 hours of participant observation. The cognitive work analysis prompt framework was used to generate a work domain analysis (WDA) and identify potential contributory factors to ADEs.

Results

The WDA identified 2 functional purposes, 7 value/priority measures, 6 purpose-related functions, 11 object-related processes and 14 objects. Structured means-ends connections supported identification of 3 potential contributory factors—resource limitations, cognitive demands, and adaptation of processes. The lack of resources (equipment, materials, knowledge, and experience) created an environment where distractions and interruptions were unavoidable. Families helped provide practical support in medicines administration but were largely unacknowledged at an organizational level. There was a lack of teamwork with regards to medication with different professionals responsible for different parts of the system. Mandated safety checks on medicines were frequently omitted because of limited resources and perceived redundancy. Interventions to support adherence to safety policies were also often bypassed because they created more work.

Conclusions

The WDA has provided insights into the complex system of medication safety for children in hospital and has facilitated the identification of potential contributory factors to ADEs. We therefore advocate (in priority order) for processes to involve parents in the care of their children in hospital, development of skill-mix interventions to ensure appropriate expertise is available where it is needed, and modified checking procedures to permit staff to use their skills and judgment effectively and efficiently.
The Versatility of Keystone Flaps for Skin Cancer Reconstruction of the Nose
Authors: Hifny Mahmoud A. , Park Tae Hwan
Published: November 2023

Nasal reconstruction has been a challenging problem for even the most experienced surgeon to provide excellent esthetic and functional outcomes. Although the bilobed flap offers distinct advantages for reconstructing these defects using an adjacent tissue with similar esthetic qualities, this flap has several potential limitations. The authors hypothesized that the conventional keystone flap and its variants provide a versatile and easily reproducible reconstructive option for nasal reconstruction after wide skin cancer excision. The authors retrospectively reviewed 12 consecutive soft tissue reconstruction data using 3 types of keystone flaps between May 2021 and July 2023. The authors reviewed all patients who underwent reconstruction with the keystone flap or its modification to repair cutaneous nasal defects following wide skin cancer excision. The authors reconstructed small- to medium-sized nasal defects ranging from 1×1 to 2.5×2.5 cm2 with a mean size of 1.2×1.1 cm2 using either a conventional keystone flap or its modification, including the Omega variant and rotation Hemi-keystone flap. All patients were satisfied with the esthetic outcomes. Keystone flaps are a versatile option for reconstructing the nose after cancer surgery. This strategy obviates the need for a bilobed flap after cancer removal in the nose.
PHYSICIANS’ ADHERENCE TO GUIDELINES ON MEDICAL THERAPY FOR HEART FAILURE AND PATIENTS’ OUTCOMES IN A KENYAN REFERRAL HOSPITAL
Authors: Mucyo Willy , Shah Jasmit , Mohamed Jeilan , Varwani Mohamed Hasham , Ngunga Mzee
Published: November 2023

Background

Adherence to guidelines on prescription and uptitration of GDMT for HFrEF is associated with reduced mortality and hospitalization. Published data on physicians’ GDMT prescription in sub-Saharan Africa is scarce. In addition, there is a need for data on patients’ characteristics, treatment, and outcomes in this region.

Objective

To determine physicians’ level of adherence to guidelines on prescription and uptitration of medical therapy for HFrEF at AKUHN, a referral hospital in Nairobi, Kenya.

Methods

We reviewed 280 files of all HFrEF patients admitted over a 3-year period. Detailed patients’ characteristics and outcomes were analyzed. We calculated the Guideline Adherence Index (GAI) and the QUality of Adherence to guideline recommendations for LIFe-saving treatment in heart failure (QUALIFY) scores. From worst to best, GAI ranges from 0 to 100%, while QUALIFY scores were categorized as poor, moderate, or good.

Results

The median age (IQR) was 63 years (53,74); 165(58.9%) were male; and 207(74.2%) were black; 98(35%) had ischemic heart disease; 153(54.6%) had hypertension, and 101(36.1%) had diabetes. At six months follow-up, 43.8% of patients had been readmitted at least once and 8.8% had died. GAI at discharge were 66.2%, 71.7%, and 42.6% for ACEI/ARNI/ARBs, B-blockers, and MRAs, respectively. At 6 months, the scores were 86.3%, 84.4%, and 61.2%, respectively. GAI for SGLT2is was 38.9% at 6 months. The proportions for good QUALIFY scores for ACEI/ARNI/ARBs, B- blockers, and MRAs were 35.8%, 38.5%, and 9.5%, respectively. Uptitration to ≥ 50% of target dose was done in 51.9%, 48.7%, and 7.9% of patients for ACEI/ARNI/ARBs, B- blockers, and MRAs, respectively.

Conclusion

Physicians’ level of adherence to prescription and up-titration of GDMT was satisfactory for ACEI/ARNI/ARBs and B-blockers, however, it was poor for SGLT2is and MRAs. There is a need for regular surveys on prescription and uptitration of GDMT with a special attention to MRAs and SGLT2is.
Automated assessments can support regional Red Lists but need to be applied with caution: A case study from central Germany
Authors: Zizka Alexander , Starke-Ottich Indra , Eichenberg David , Bönsel Dirk , Zizka Georg
Published: November 2023

Aim

Expert-based regional Red Lists (RL) carry conservation legislation globally. Yet, they are often difficult to reproduce and their regular compilation by a dwindling number of expert assessors burdens many regional conservation authorities. Here we batch-estimate RL indicators and extinction risk for >1,100 plant species and test the potential of this automated approach to support the expert-based RL process.

Location

State of Hesse, Central Germany

Methods

First, we estimated current population status, short-term population trend, long-term population trend, and extinction risk by binning existing occurrence probabilities modelled at three time slices with cut-off values derived from RL methodology. Subsequently we compared the results with the latest version of the Hessian expert-based RL using summary statistics and selected example species.

Results

We find the assessments of extinction risk to agree in c. 60% of the cases, mostly for species not threatened with extinction. Existing mismatch was by one category in most cases, but up to 6 categories in some cases (mean: 1.6 categories). Furthermore, agreement was highest for extreme categories and very abundant species.

Main conclusions

Automated assessments were simplistic for many rare and taxonomically challenging species, but we considered them more accurate than the expert assessments for species with intermediate population size and for species of anthropogenic habitats. Furthermore, the automated assessments are particularly informative for the estimation of long-term and short-term population trends, for which experts are often left to guesstimate based on little data.
Story of an infection: viral dynamics and host responses in theCaenorhabditis elegans-Orsay virus pathosystem
Authors: Castiglioni Victoria G. , Olmo-Uceda Maria J. , Villena-Giménez Ana , Muñoz-Sánchez Juan C. , Elena Santiago F.
Published: November 2023

Orsay virus (OrV) is the only known natural virus affectingCaenorhabditis elegans, with minimal impact on the worm’s fitness due to its robust innate immune response. This study aimed to understand the interactions betweenC. elegansand OrV by tracking the infection’s progression during larval development. Four distinct stages of infection were identified based on viral load, with a peak in capsid- encoding RNA2 coinciding with the first signs of viral egression. Transcriptomic analysis revealed temporal changes in gene expression and functions induced by the infection. A specific set of up- regulated genes remained active throughout the infection, and genes correlated and anticorrelated with virus accumulation were identified. Responses to OrV mirrored reactions to other biotic stressors, distinguishing between virus-specific responses and broader immune responses. Additionally, mutants of early response genes and defense-related processes showed altered viral load progression, uncovering new players in the antiviral defense response.
Taking fear back into the Marginal Value Theorem: the risk-MVT and optimal boldness
Authors: Calcagno Vincent , Grognard Frédéric , Hamelin Frédéric M. , Mailleret Ludovic
Published: November 2023

Foragers exploiting heterogeneous habitats must make strategic movement decisions in order to maximize fitness. Foraging theory has produced very general formalizations of the optimal patch-leaving decisions rational individuals should make. One is Charnov’s Marginal Value Theorem (MVT), which models the sequential visit of habitat patches and their spatial distribution. The MVT has a simple intuitive graphical interpretation in terms of gain functions and travel times. However, it considers only energy gains, and the effect of predation risk on the time allocation strategy is notoriously lacking. An important development that includes predation risk was Brown’s economic treatment of optimal patch leaving decisions, the basis of giving-up density (GUD) theory, often cited as an extension of the MVT. However, it is a more abstract result that does not have the specificities or graphical appeal of the MVT. Although both successful, the two theories are cited by distinct communities and are seldom connected in texbooks. Here we formally introduce the risk-MVT (rMVT), a generalization of the MVT that can incorporate most types of predation risks. We show that Brown’s GUD-theory is equivalent to a rMVT, but applies for one type of predation risk only. The rMVT retains the structure and graphical simplicity of the MVT, but implies a shift from residence time to expected dose of risk (micromort units, as used in decision analysis) as the domain over which rates of gain are computed and maximized. Applications of the rMVT show that different types of risk can yield opposite responses of optimal strategies to an increase in the risk level, and predict differential responses of behaviours observed in experimental versus natural conditions. The risk-MVT can also be used to predict the optimal level of risk taking, or “optimal boldness”, and suggests that individuals should generally be bolder in riskier habitats.
DeepCor: Denoising fMRI Data with Contrastive Autoencoders
Authors: Zhu Yu , Aglinskas Aidas , Anzellotti Stefano
Published: November 2023

Functional magnetic resonance imaging (fMRI) is widely used in neuroscience research. FMRI data is noisy; improving denoising methods could lead to novel discoveries. Here, we introduce and evaluate a denoising method (DeepCor) which utilizes deep generative models to disentangle and remove noise. DeepCor outperforms CompCor (a state-of-the art denoising approach) on a variety of simulated datasets. In addition, DeepCor enhances differences in connectivity between brain networks in real datasets.
Non-linear modelling of motor development in typically developing children and youth using robotic assessments
Authors: Dobri Stephan C.D. , Scott Stephen H. , Davies T. Claire
Published: November 2023

Background

Clinical tasks are most often used to differentiate motor performance of individuals who have impaired function. However, these are not as accurate and repeatable as robotic tasks. Additionally, motor development occurs rapidly at early ages and slows as they reach adulthood, resulting in a non-linear model of performance. There is also evidence that variability in performance changes as children and youth age. Accurate normative models of performance are necessary to identify differentiate deficiencies in motor performance and to track the efficacy of therapies.

Methods

Two-hundred and eighty-eight participants who are typically developing (ages 5-18) completed a robotic point-to-point reaching task and an object hitting task using the Kinarm Exoskeleton. Exponential or quadratic curves were fit to performance parameters generated by Kinarm to model typical performance. These models included a linear term to account for changing variability with age.

Results

Most performance parameters showed improvement with age, and none showed deterioration. Some parameters showed large changes in variability in performance with age, up to a 74% decrease in the range of typical performance.

Conclusions

Reduced variability occurs with age, indicating the need to account for differences in variability when developing models of typical motor performance in children and youth. Models used to identify deficits in motor performance should account for changing variability in data and changing repeatability with age to increase accuracy of identification of deficits.
Characterization of groups of informal caregivers. A cluster analysis using the example of Saxony
Authors: Tischendorf Tim , Geithner Silke , Schaal Tom
Published: November 2023

Background

As a result of demographic change, a further increase in the number of people in need of care in Germany can be expected in the future. Nursing activities performed by family members are a central component of care provision. The assumption of support services is increasingly associated with an additional physical and psychological burden on informal caregivers. The aim of this study is to identify and characterize groups of informal caregivers with regard to their well-being.

Methodology

The empirical study was based on a survey on home care in Saxony from 2019, which was intended as exploratory work to provide insights into the care situation in Saxony. The central component is a two-step cluster analysis with exclusively informal caregivers.

Results

The net sample size for the cluster analysis comprised 178 subjects who were involved in caring for relatives. The cluster analysis revealed two groups of caregiving relatives in Saxony, which were differentiated by a different experience of stress and various sociodemographic factors.

Discussion

Informal caregivers in Saxony are not a homogeneous group. Depending on various sociodemographic factors or the care effort and situation, they are confronted with different challenges in caring for relatives, which are directly reflected in their well-being. In order to achieve a targeted reduction in the burden on family caregivers, cooperation and constructive collaboration between political decision-makers, care and health insurers, and the various players in health and care provision is required.