bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of expression of molecular chaperones
Authors: Lund Peter A 
Published: November 2023

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractAlzheimer'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.
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

ABSTRACT
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

ABSTRACTBackground: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.
Lessons learned in translating pain knowledge into practice
Authors: Becker Juliane , Effraim Philip R. , Dib-Hajj Sulayman , Rittner Heike L. 
Published: November 2023

Abstract

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

AbstractNeuropathic 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.