bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency of IKKβ in neurons ameliorates Alzheimer's disease pathology in APP‐ and tau‐transgenic mice
Authors: Schnöder Laura , Quan Wenqiang , Yu Ye , Tomic Inge , Luo Qinghua , Hao Wenlin , Peng Guoping , Li Dong , Fassbender Klaus , Liu Yang 
Published: January 2023

AbstractIn Alzheimer's disease (AD) brain, inflammatory activation regulates protein levels of amyloid‐β‐peptide (Aβ) and phosphorylated tau (p‐tau), as well as neurodegeneration; however, the regulatory mechanisms remain unclear. We constructed APP‐ and tau‐transgenic AD mice with deletion of IKKβ specifically in neurons, and observed that IKKβ deficiency reduced cerebral Aβ and p‐tau, and modified inflammatory activation in both AD mice. However, neuronal deficiency of IKKβ decreased apoptosis and maintained synaptic proteins (e.g., PSD‐95 and Munc18‐1) in the brain and improved cognitive function only in APP‐transgenic mice, but not in tau‐transgenic mice. Additionally, IKKβ deficiency decreased BACE1 protein and activity in APP‐transgenic mouse brain and cultured SH‐SY5Y cells. IKKβ deficiency increased expression of PP2A catalytic subunit isoform A, an enzyme dephosphorylating cerebral p‐tau, in the brain of tau‐transgenic mice. Interestingly, deficiency of IKKβ in neurons enhanced autophagy as indicated by the increased ratio of LC3B‐II/I in brains of both APP‐ and tau‐transgenic mice. Thus, IKKβ deficiency in neurons ameliorates AD‐associated pathology in APP‐ and tau‐transgenic mice, perhaps by decreasing Aβ production, increasing p‐tau dephosphorylation, and promoting autophagy‐mediated degradation of BACE1 and p‐tau aggregates in the brain. However, IKKβ deficiency differently protects neurons in APP‐ and tau‐transgenic mice. Further studies are needed, particularly in the context of interaction between Aβ and p‐tau, before IKKβ/NF‐κB can be targeted for AD therapies.
Quality indicators for anesthesia and perioperative medicine
Authors: Wacker Johannes 
Published: January 2023

Purpose of review
Routine monitoring of care quality is fundamental considering the high reported rates of preventable perioperative morbidity and mortality. However, no set of valid and feasible quality indicators is available as the gold standard for comprehensive routine monitoring of the overall quality of perioperative care. The purpose of this review is to describe underlying difficulties, to summarize current trends and initiatives and to outline the perspectives in support of suitable perioperative quality indicators.

Recent findings
Most perioperative quality indicators used in the clinical setting are based on low or no evidence. Evidence-based perioperative quality indicators validated for research purposes are not always applicable in routine care. Developing a core set of perioperative quality indicators for clinical practice may benefit from matching feasible routine indicators with evidence-based indicators validated for research, from evaluating additional new indicators, and from including patients’ views.

Summary
A core set of valid and feasible quality indicators is essential for monitoring perioperative care quality. The development of such a set may benefit from matching evidence-based indicators with feasible standard indicators and from including patients’ views.
Endogenous dehydroepiandrosterone and depression in postmenopausal women: a systematic review of observational studies
Authors: Hemachandra Chandima , Davis Susan R. , Bell Robin J. , Sultana Farhana , Islam Rakibul M. 
Published: January 2023

Abstract

Importance
The associations between endogenous dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), and depression in older women are uncertain. However, DHEA supplements are widely available over the counter in some countries, and some people may be taking DHEA with the hope of positive mood effects.

Objective
This systematic review aimed to investigate the association between endogenous DHEA/DHEAS blood concentrations and depression/depressive symptoms in community-dwelling postmenopausal women.

Evidence Review
Searches were conducted in Ovid MEDLINE, EMBASE, PsycINFO, and Web of Science databases for observational studies with at least 100 community-dwelling participants until March 9, 2022. The bibliographies of retrieved articles were manually searched. The studies published in English and meeting the inclusion criteria were included in the review. The risk of bias was assessed with the modified Hoy tool for cross-sectional designs and the Joanna Briggs Institute modified critical appraisal checklist for cohort studies.

Findings
Of the 30 articles retrieved for full-text review, 14 met the criteria for inclusion. Seven studies were cross-sectional, six were longitudinal, and one had both cross-sectional and longitudinal data. Five of eight cross-sectional studies found no association between DHEAS and depression, whereas three studies reported an inverse association. Similarly, most of the studies (n = 4) with longitudinal data reported no association, whereas two studies reported either an inverse association or mixed results for DHEAS and depression severity. No association between DHEA and depression was found irrespective of the study design. Heterogeneity of design was a barrier to meta-analysis and between study comparison. The majority of studies were limited by high risk of bias in at least one assessed domain.

Conclusion and Relevance
This systematic review does not support an association between endogenous DHEA/DHEAS and depression in postmenopausal women.
Impacts of HER2 immunohistochemical scores on response and outcomes of HER2-positive breast cancers after neoadjuvant therapy
Authors: Chiu Yun-Ning , Hsu Chih-Yi , Lien Pei-Ju , Chao Ta-Chung , Liu Chun-Yu , Lin Yen-Shu , Wang Yu-Ling , Tsai Yi-Fang , Tseng Ling-Ming 
Published: January 2023

Background:
Neoadjuvant systemic therapy (NST) is conducted in increased number of patients with breast cancer overexpressing human epidermal growth factor receptor 2 (HER2). Whether the intensity of HER2 protein expression determines response to treatment is challenged. This study aims to analyze the impact of HER2 immunohistochemical (IHC) scores on NST response and survival outcome.

Methods:
We analyzed a total of 197 patients with HER2-positive breast cancer receiving NST and definite surgery from a prospectively collected database. The analyzed endpoints included pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). More patients with IHC 2+/in situ hybridization (ISH)-positive tumors presented positive for hormonal receptors, compared with those with IHC 3+ tumors. No clinicopathological features except tumor necrosis were significantly associated with pCR.

Results:
Both positive hormone receptors and IHC scores stood on the borderline in statistical analysis. IHC 3+ group tends to present a higher pCR rate than IHC 2+/ISH+ groups (52.5% vs. 34.3%). Patients who achieved pCR had better survival outcome than that of non-pCR group. The impact of pCR on survival reached the statistical significance in the IHC 3+ group both in DFS (90.9% vs. 76.5%; p = 0.004) and OS (97.4% vs. 83.2%; p = 0.002). Multivariate analysis demonstrated IHC scores as an independent predictor of survival outcome with the adjustment of tumor staging and pCR.

Conclusion:
HER2 IHC score is an independent predictor for outcome. IHC 3+ tumors presented a trend of higher pCR rate and better outcome in HER2-positive breast cancer patients who receive NST.
Hypertension in Pregnancy: What We Now Know
Authors: Gupta Sonali , Petras Lohana , Tufail Muhammad Umer , Rodriguez Salazar Juan Diego , Jim Belinda 
Published: January 2023

Purpose of review
Hypertensive disorders of pregnancy remain a highly morbid condition that affects both the mother and fetus, complicate approximately 10% of pregnancies worldwide, and contribute to immediate and long-term cardiovascular outcomes. There is still much to learn regarding pathogenesis and treatment goals.

Recent findings
There is updated information on the pathogenesis of preeclampsia and treatment thresholds for HTN in pregnancy. l-Kynurenine, a metabolite of the essential amino acid l-tryptophan, has been implicated in preeclampsia as decreased levels were found in a uninephrectomized pregnant mouse model of preeclampsia, where replacement of l-kynurenine rescued the preeclamptic state. Further, data from CHIPS (The Control of HTN in Pregnancy Study) and CHAP (Chronic HTN and Pregnancy) trials demonstrate not only the safety of lowering blood pressure to either a diastolic goal of 85 mmHg (CHIPS) or less than 160/105 mmHg (CHAP) without detriment to the fetus but the CHAPS trial has also shown a decrease in the rate of preeclampsia in the treatment group.

Summary
We will summarize the different types of hypertensive disorders in pregnancy, updates on the pathogenesis of preeclampsia, and appropriate HTN management based on the latest evidence in order to better care for mother and child.
Type 4 renal tubular acidosis and uric acid nephrolithiasis: two faces of the same coin?
Authors: Adomako Emmanuel A. , Maalouf Naim M. 
Published: January 2023

Purpose of review
The present review summarizes findings of recent studies examining the epidemiology, pathophysiology, and treatment of type 4 renal tubular acidosis (RTA) and uric acid nephrolithiasis, two conditions characterized by an abnormally acidic urine.

Recent findings
Both type 4 RTA and uric acid nephrolithiasis disproportionately occur in patients with type 2 diabetes and/or chronic kidney disease. Biochemically, both conditions are associated with reduced renal ammonium excretion resulting in impaired urinary buffering and low urine pH. Reduced ammoniagenesis is postulated to result from hyperkalemia in type 4 RTA and from insulin resistance and fat accumulation in the renal proximal tubule in uric acid nephrolithiasis. The typical biochemical findings of hyperkalemia and systemic acidosis of type 4 RTA are rarely reported in uric acid stone formers. Additional clinical differences between the two conditions include findings of higher urinary uric acid excretion and consequent urinary uric acid supersaturation in uric acid stone formers but not in type 4 RTA.

Summary
Type 4 RTA and uric acid nephrolithiasis share several epidemiological, clinical, and biochemical features. Although both conditions may be manifestations of diabetes mellitus and thus have a large at-risk population, the means to the shared biochemical finding of overly acidic urine are different. This difference in pathophysiology may explain the dissimilarity in the prevalence of kidney stone formation.
Survey of Adolescents' and Emerging Adults' Preferences for Gonorrhea and Chlamydia Testing in Primary Care
Authors: Reingold Sarah , Tomcho Margaret , Thomas-Gale Tara , Haynes Christine , O'Leary Sonja , Warsh Sarah , Rinehart Deborah , Frost Holly 
Published: January 2023

Abstract
Our study assessed adolescents' and emerging adults' (ages 14–24 years) preferences for opt-out gonorrhea and chlamydia screening compared with risk-based screening. Most participants (93%) preferred opt-out gonorrhea and chlamydia testing compared with risk-based testing (6%), and opt-out testing was associated with less sexually transmitted infection–related stigma (P < 0.05).
Rasch validation of the German translation of the Prosthetic Limb Users Survey of Mobility short forms in people with lower limb amputation
Authors: Bekrater-Bodmann Robin , Kehl Isabelle , Hafner Brian J. , Ranker Alexander , Giordano Andrea , Franchignoni Franco 
Published: January 2023

Background:
Prostheses are a primary rehabilitative intervention for people after lower limb amputation. To appropriately measure the effectiveness of prosthetic interventions, valid and reliable measures of prosthetic mobility are required. The Prosthetic Limb Users Survey of Mobility (PLUS-M) is a promising instrument for measuring prosthesis users' mobility. However, German translations of the PLUS-M short forms have not yet been validated.

Objectives:
Rasch validation of the German translation of the PLUS-M short forms in people with lower limb amputation.

Study design:
This study is based on a cross-sectional survey of prosthesis-using lower limb amputees from a nation-wide cohort.

Methods:
PLUS-M data (the 7-item and the 12-item shortforms; PLUS-M-7 and PLUS-M-12, respectively) from 194 lower limb prosthesis users were subjected to Rasch analysis, an advanced statistical method for assessing if the measurement properties of a questionnaire comply with a wide spectrum of psychometric requirements.

Results:
Analysis showed appropriate rating scale functioning, good internal construct validity (item fit), unidimensionality, and good targeting of the PLUS-M-7 and PLUS-M-12 short forms. Moreover, the greater conditional measurement precision of PLUS-M-12 (regarding higher test information and lower standard error of mobility estimates) was quantified.

Conclusions:
Rasch analysis of the German translation of both PLUS-M short forms showed good psychometric qualities. In addition, our study showed that test scores from the PLUS-M-12 are more accurate. Therefore, the PLUS-M-12 is recommended for individual-level clinical applications (e.g., classification or change assessment).
Effects of Conditioned Medium of Adipose-Derived Stem Cells Exposed to Platelet-Rich Plasma on the Expression of Endothelial Nitric Oxide Synthase and Angiogenesis by Endothelial Cells
Authors: Morita Maki , Suyama Yoshiko , Notsu Tomomi , Fukuoka Kohei , Ikuta Kento , Kanayama Haruka , Umeda Ryunosuke , Teraoka Shogo , Minato Hiroyuki , Ninomiya Haruaki , Tsuneto Motokazu , Shirayoshi Yasuaki , Hisatome Ichiro , Yagi Shunjiro 
Published: January 2023

AbstractPlatelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) are known to secrete angiogenic factors that contribute to the treatment of intractable ulcers. The combination of PRP and ADSCs may enhance their angiogenic effects. However, it remains unclear whether treatment of ADSCs with PRP influences angiogenesis. We studied whether the conditioned medium from PRP-treated ADSCs under hypoxic conditions exerts angiogenic effects. Although PRP stimulated the proliferation of ADSCs obtained from rats, it decreased the mRNA levels of vascular endothelial growth factor, hepatocyte growth factor, and TGF-β1, but not of basic fibroblast growth factor, under hypoxia. The conditioned medium of PRP-treated ADSCs inhibited endothelial nitric oxide synthase phosphorylation, decreased NO production, and suppressed tube formation in human umbilical vein endothelial cells. Transplantation of ADSCs alone increased both blood flow and capillary density of the ischemic limb; however, its combination with PRP did not further improve blood flow or capillary density. This suggests that both conditioned medium of ADSCs treated with PRP and combination of PRP with ADSCs transplantation may attenuate the phosphorylation of endothelial nitric oxide synthase and angiogenesis.
Comparison of Lymphatic Drainage of the Lower Limbs After Soft Tissue Reconstruction by Microvascular Muscle Flap Versus Fasciocutaneous Flaps
Authors: Cordelia M.J. Felix , Ete Geley , Paul M. Kingsly , Akamanchi Anirudha K. , Hephzibah Julie , Benjamin Justin , Agarwal Shwetha 
Published: January 2023

Introduction
Complex traumatic injuries of the lower limb are increasingly being salvaged. The common long-term morbidity includes secondary lymphedema. The role of microvascular flaps is often discussed for lymph flow restoration. However, the differential effect of using muscle flap versus fasciocutaneous flap in the lower-limb trauma to avoid secondary lymphedema is not studied.

Methods
Forty patients who underwent microvascular flap reconstruction were reviewed retrospectively to obtain data regarding clinical demographics and surgical procedure. Assessment for presence of clinical lymphedema was done. The lymphatic drainage in all these patients was assessed by 99mTc lymphoscintigraphy.

Results
Of the 40 patients included in the study, group A (n = 23) underwent muscle-based free flap reconstruction, and group B (n = 17) had fasciocutaneous flaps. Clinical lymphedema was present in 21 patients, of which 18 were of group A and 3 of group B. On lymphoscintigraphy, 14 patients had either partial or complete obstruction in the reconstructed lower limb, 11 in group A and 3 in group B. All of them (n = 14) were found to have associated clinical lymphedema. The association of clinical lymphedema (P < 0.001) and obstructive pattern on lymphoscintigraphy (P < 0.05) with muscle flaps was found to be statistically significant.

Conclusions
With the advancement in surgery and techniques, not only salvageability but also stable and morbidity free outcomes are the goals. Fasciocutaneous flaps may have better lymphatic outcomes than the muscle-based flaps, and the criteria for lower-limb reconstruction can be reformed to include simultaneous soft tissue and lymphatic reconstruction.
The Progression of Interstitial Fibrosis and Tubular Atrophy at 6 Months Is an Independent Predictor of Poor Graft Outcomes in Kidney Transplant Recipients
Authors: Ouellet Gabriel , Houde Isabelle , Riopel Julie , Latulippe Eva , Douville Pierre , Lesage Julie , Côté Isabelle , Lapointe Isabelle , De Serres Sacha A. 
Published: January 2023

Background.
Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined.

Methods.
We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients.

Results.
The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff “i”) score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were.

Conclusions.
Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection.
Assessment of dd-cfDNA Levels in Clinically Stable Lung Allograft Recipients Beyond the Initial 2 y Posttransplant
Authors: Trindade Anil J. , Chapin Kaitlyn C. , Mullican Amy , Gray Jennifer N. , Hoy Haley , Demarest Caitlin T. , Lambright Eric S. , McPherson Katie A. , Norfolk Stephanie G. , Robbins Ivan M. , Bacchetta Matthew , Erasmus David B. , Shaver Ciara M. 
Published: January 2023

Background.
Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker for the diagnosis of acute allograft injury within the first 1 to 2 y after lung transplant, but its utility for diagnosing chronic lung allograft dysfunction (CLAD) has not yet been studied. Understanding baseline dd-cfDNA kinetics beyond the initial 2 y posttransplant is a necessary first step in determining the utility of dd-cfDNA as a CLAD biomarker. We seek to establish baseline dd-cfDNA% levels in clinically stable lung allograft recipients who are >2 y posttransplant.

Methods.
We performed a prospective, single-center, observational study to identify plasma dd-cfDNA levels in clinically stable lung allograft recipients >2 y posttransplant.

Results.
Fifty-one subjects were enrolled and ≥3 baseline dd-cfDNA measurements were acquired during a median of 252 d. The median baseline percent dd-cfDNA level in our cohort was 0.45% (interquartile range [IQR], 0.26–0.69). There were statistically significant differences in dd-cfDNA based on posttransplant duration (≤5 y posttransplant median 0.41% [IQR, 0.21–0.64] versus >5 y posttransplant median 0.50% [IQR, 0.33–0.76]; P < 0.02). However, the clinical significance of this small change in dd-cfDNA is uncertain because this magnitude of change is within the biologic test variation of 73%.

Conclusions.
This study is the first to define levels of dd-cfDNA in clinically stable patients who are >2 y post–lung transplant. These findings lay the groundwork for the study of dd-cfDNA as a possible biomarker for CLAD.
Evolutionary ecology of language origins through confrontational scavenging
Authors: Szilágyi András , Kovács Viktor P. , Czárán Tamás , Szathmáry Eörs 
Published: January 2023

A dynamic model and an agent-based simulation model implementing the assumptions of the confrontational scavenging hypothesis on early protolanguage as an adaptive response ofHomo erectusto gradual change in their habitat has been developed and studied. The core assumptions of the hypothesis and the model scenario are the pre-adaptation of our ancestors to occupy the ecological niche that they constructed for themselves by having evolved displaced communication and a rudimentary tool manufacture, two features allowing them to use a new, concentrated and abundant resource—megafauna carrion—on the savannahs replacing arboreal habitats owing to the drying climate of East Africa at about 2 Ma. The shift in diet required coordinated cooperation by the hominin scavengers confronted with concurrent predators. Power scavenging compelled displaced symbolic communication featuring a limited semantic range; syntax was not yet required. We show that phenotypic evolution on the accuracy of information transfer between cooperating hominins is a necessary and sufficient condition for the population of agents to survive the diet shift. Both the individual and the group fitness of the hominin horde increased with the accuracy of their protolanguage, with decreasing time allocated to foraging and thus more time left for culture.This article is part of the theme issue ‘Human socio-cultural evolution in light of evolutionary transitions’.
Can models of evolutionary transition clarify the debates over the Neolithic Revolution?
Authors: Shavit Ayelet , Sharon Gonen 
Published: January 2023

The ‘Neolithic Revolution,’ sometimes referred to as the emergence of agriculture at its earliest in the southern Levant, is the most significant shift in human history, shaping the world we live in today. Yet, after 100 years of study, its major cause, tempo (gradual or revolutionary), and impact of human intentionality remain disputed. Here, we examine the research potential of an evolutionary transition in individuality (ETI) to clarify this dramatic shift. Applying an ETI research perspective reveals how different causes and conditions lead to the same result, enabling a holistic view rather than a reduction of ‘Neolithic' to ‘agriculture,' or to one major climatic condition, inheritance system or standard evolutionary model, thus allowing us to clarify and bypass some of these heated, unresolved disputes. Additionally, unlike current archaeological emphasis on ‘where,' ‘when,' ‘why' and ‘how' questions, the ETI perspective offers a productive path for resolving a fundamental preliminary anomaly: why and how could the Neolithic lifeway evolve at all, given the selfish interest of individuals in a hunter–gatherer group? We do not intend to solve the shift to Neolithic lifeways, only to offer a fresh lens for examining it, emphasizing the relevance of tracking within and between group differences.
This article is part of the theme issue ‘Human socio-cultural evolution in light of evolutionary transitions’.