bluuebunny/crossref_metadata_2025 huggingface dataset:
Geriatrie: Was ist normal im Alter? Stehen wir vor einem Paradigmenwechsel in der Laboratoriumsmedizin? / Geriatrics: What is normal in the aged? Should we expect a paradigm shift in laboratory medicine?
Authors: Lapin Alexander
Published: February 2007

Die wachsende Bedeutung der Geriatrie stellt die Labordiagnostik vor neue Herausforderungen. Gleichzeitig besteht die Notwendigkeit grundlegende Prinzipien, wie das „Referenzintervallkonzept“ neu zu überdenken. Da in der Geriatrie die individuelle Lebensqualität vor dem allgemeinen Gesundheitsbegriff steht, soll die Befundbewertung nicht nur in Bezug auf das Gesundenkollektiv, sondern auch nach Vorwerten, im Sinne des individuellen Monitorings erfolgen. Daraus ergeben sich besondere Anforderungen an die Qualitätssicherung, Laborlogistik sowie Berücksichtigung der Präanalytik. Im Hinblick auf die jeweilige Lebenserwartungsprognose, können sich medizinische Aussagen von vielen Laborparametern im Alter verändern. Den Parametern, die Auskunft über die noch vorhandene physiologische Funktionsreserven geben, kommt aus klinischer Sicht eine besondere Bedeutung zu.
Self-Renewing and Differentiating Properties of Cortical Neural Stem Cells Are Selectively Regulated by Basic Fibroblast Growth Factor (FGF) Signaling via Specific FGF Receptors
Authors: Maric Dragan , Fiorio Pla Alessandra , Chang Yoong Hee , Barker Jeffery L.
Published: February 2007

Developmental processes mediating the initiation of lineage commitment from self-renewing neural stem cells (NSCs) remain mostly unclear because of the persisting ambiguity in identifying true NSCs from proliferative lineage-restricted progenitors (LRPs), which are directly or indirectly derived from NSCs. Our multilineage immunohistochemical analyses of early embryonic rat telencephalon at the onset of neurogenesis revealed clear dorsoventral gradients in the emergence of two types of neuronal progenitors (NPs) from multilineage-negative NSCs. Enumeration of NSCs using comprehensive flow cytometric analysis demonstrated that their precipitous declinein vivoinvolved both active differentiation into NPs and an increased propensity toward apoptosis. Both processes paralleled the dorsoventral changes in fibroblast growth factor receptor (FGFR) expressions. NSCs residing in the dorsal telencephalon coexpressed FGFR1 and FGFR3, whereas those residing in the ventral telencephalon also expressed FGFR2. NSCs exposed to basic fibroblast growth factor (bFGF)in vitrogenerated four stereotypical clonal expansion states: efficiently self-renewing, inefficiently self-renewing limited by apoptosis, exclusively neurogenic, and multipotential, generating up to five types of LRPs. The plasticity among these expansion states depended on ambient [bFGF], telencephalic developmental stage, and differential activation/inactivation of specific FGFRs. Coactivation of FGFR1 and FGFR3 promoted symmetrical divisions of NSCs (self-renewal), whereas inactivation of either triggered asymmetrical divisions and neurogenesis from these cells. Developmental upregulation of FGFR2 expression correlated with a shift of NSCs into a multipotential state or apoptosis. These results provide new insights regarding the roles of FGFRs in diversification of NSC properties and initiation of neural lineage-restricted differentiation.
A Developmental Switch to GABAergic Inhibition Dependent on Increases in Kv1-Type K+Currents
Authors: Howard MacKenzie A. , Burger R. Michael , Rubel Edwin W
Published: February 2007

Mature nucleus magnocellularis (NM) neurons, the avian homolog of bushy cells of the mammalian anteroventral cochlear nucleus, maintain high [Cl−]iand depolarize in response to GABA. Depolarizing GABAergic postsynaptic potentials (GPSPs) activate both the synaptic conductance and large outward currents, which, when coupled together, inhibit spikes via shunting and spike threshold accommodation. We studied the maturation of the synaptic and voltage-dependent components of inhibition in embryonic NM neurons using whole-cell and gramicidin-perforated patch-clamp techniques to measure Cl−reversal potential, GABAergic synaptic responses, and voltage-dependent outward currents. We found that GABA enhanced excitability in immature NM neurons, undergoing a switch to inhibitory between embryonic day 14 (E14) and E18. Low-voltage-activated Kv1-type (dendrotoxin-I sensitive) K+currents increased in amplitude between E14 and E18, whereas Cl−reversal potential and synaptic conductances remained relatively stable during this period. GABA was rendered inhibitory because of this increase in low-voltage activated outward currents. GPSPs summed with other inputs to increase spike probability at E14. GPSPs shunted spikes at E18, but blocking Kv1 channels transformed this inhibition to excitation, similar to E14 neurons. Subthreshold depolarizing current steps, designed to activate outward currents similar to depolarizing GPSPs, enhanced excitability at E14 but inhibited spiking in E18 neurons. Blocking Kv1 channels reversed this effect, rendering current steps excitatory. We present the novel finding that the developmental transition of GABAergic processing from increasing neuronal excitability to inhibiting spiking can depend on changes in the expression of voltage-gated channels rather than on a change in Cl−reversal potential.
Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis
Authors: Shacka John J. , Klocke Barbara J. , Young Chainllie , Shibata Masahiro , Olney John W. , Uchiyama Yasuo , Saftig Paul , Roth Kevin A.
Published: February 2007

Neuronal ceroid lipofuscinosces/Batten disease (NCL) is a devastating group of neurodegenerative diseases caused by genetic disruptions in lysosomal function. Cathepsin D (CD) is a major lysosomal protease, and mutations in CD that render it enzymatically defective have been reported recently in subsets of NCL patients. The targeted deletion of CD in mice results in extensive neuropathology, including biochemical and morphological evidence of apoptosis and autophagic stress (aberrant autophagosome accumulation), effects that are similar to those observed in NCL. To determine the contribution of Bax-dependent apoptosis in this mouse model of NCL, combined Bax- and CD-deficient mice were generated. Morphological analysis of CD-deficient mouse brains indicated large numbers of pyknotic neurons and neurons with marked cytoplasmic swellings containing undigested lipofuscin. Cell death and apoptosis were evidenced by increases in terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) reactivity and activation of caspase-3, respectively. DeOlmos silver-positive neurons were abundant in CD-deficient brain and correlated with neuron loss, as indicated by significant decreases in NeuN (neuronal nuclear antigen)-positive neurons. Lysosome dysfunction and autophagic stress were apparent in CD-deficient brain as indicated by the accumulation of autofluorescent storage material and by increased levels of LC3-II (light chain 3-II, a selective autophagosome marker), respectively. Bax deletion significantly inhibited caspase-3 activation and hippocampal TUNEL reactivity but did not prevent the majority of CD deficiency-induced neuropathology, including the persistence of pyknotic neurons, elevated cortical TUNEL reactivity, lysosome dysfunction and autophagic stress, neurodegeneration, and neuron loss. Together, these results suggest that CD deficiency-induced neuropathology does not require Bax-dependent apoptosis and highlights the importance of caspase-independent neuron death and neurodegeneration resulting from the genetic disruption of lysosome function.
Validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Rheumatoid Arthritis: The Perspective of Physical Therapists
Authors: Kirchberger Inge , Glaessel Andrea , Stucki Gerold , Cieza Alarcos
Published: February 2007

Background and Purpose

The Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Rheumatoid Arthritis (RA) represents the typical spectrum of problems in the functioning of patients with RA. The objective of this study was to validate this ICF Core Set from the perspective of physical therapists.

Methods

Physical therapists were asked about their intervention goals in a 3-round Delphi survey. Intervention goals were compiled, and the physical therapists were asked whether they considered the goal classes to be relevant. The goal classes then were linked to the ICF.

Results

A total of 82 physical therapists in 12 countries named 562 intervention goals. A total of 45 goal classes covering all ICF components were identified. The goal classes addressing muscle tone, balance and coordination, and psychological distress were not represented in the ICF Core Set for RA.

Discussion and Conclusion

The validity of the ICF Core Set for RA was largely supported. However, some categories currently not covered by the ICF Core Set for RA will need to be investigated further.
Primary Care Interventions to Prevent Child Maltreatment
Authors: Viswanathan Meera , Rains Caroline , Hart Laura C. , Doran Emma , Sathe Nila , Hudson Kesha , Ali Rania , Jonas Daniel E. , Chou Roger , Zolotor Adam J.
Published: March 2024

Importance

Child maltreatment is associated with serious negative physical, psychological, and behavioral consequences.

Objective

To review the evidence on primary care–feasible or referable interventions to prevent child maltreatment to inform the US Preventive Services Task Force.

Data Sources

PubMed, Cochrane Library, and trial registries through February 2, 2023; references, experts, and surveillance through December 6, 2023.

Study Selection

English-language, randomized clinical trials of youth through age 18 years (or their caregivers) with no known exposure or signs or symptoms of current or past maltreatment.

Data Extraction and Synthesis

Two reviewers assessed titles/abstracts, full-text articles, and study quality, and extracted data; when at least 3 similar studies were available, meta-analyses were conducted.

Main Outcomes and Measures

Directly measured reports of child abuse or neglect (reports to Child Protective Services or removal of the child from the home); proxy measures of abuse or neglect (injury, visits to the emergency department, hospitalization); behavioral, developmental, emotional, mental, or physical health and well-being; mortality; harms.

Results

Twenty-five trials (N = 14 355 participants) were included; 23 included home visits. Evidence from 11 studies (5311 participants) indicated no differences in likelihood of reports to Child Protective Services within 1 year of intervention completion (pooled odds ratio, 1.03 [95% CI, 0.84-1.27]). Five studies (3336 participants) found no differences in removal of the child from the home within 1 to 3 years of follow-up (pooled risk ratio, 1.06 [95% CI, 0.37-2.99]). The evidence suggested no benefit for emergency department visits in the short term (<2 years) and hospitalizations. The evidence was inconclusive for all other outcomes because of the limited number of trials on each outcome and imprecise results. Among 2 trials reporting harms, neither reported statistically significant differences. Contextual evidence indicated (1) widely varying practices when screening, identifying, and reporting child maltreatment to Child Protective Services, including variations by race or ethnicity; (2) widely varying accuracy of screening instruments; and (3) evidence that child maltreatment interventions may be associated with improvements in some social determinants of health.

Conclusion and Relevance

The evidence base on interventions feasible in or referable from primary care settings to prevent child maltreatment suggested no benefit or insufficient evidence for direct or proxy measures of child maltreatment. Little information was available about possible harms. Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment.
Primary Care Interventions to Prevent Child Maltreatment
Authors:   US Preventive Services Task Force, Barry Michael J. , Nicholson Wanda K. , Silverstein Michael , Chelmow David , Coker Tumaini Rucker , Davis Esa M. , Jaén Carlos Roberto , Krousel-Wood M. (Tonette) , Lee Sei , Li Li , Rao Goutham , Ruiz John M. , Stevermer James J. , Tsevat Joel , Underwood Sandra Millon , Wiehe Sarah
Published: March 2024

Importance

Child maltreatment, which includes child abuse and neglect, can have profound effects on health, development, survival, and well-being throughout childhood and adulthood. The prevalence of child maltreatment in the US is uncertain and likely underestimated. In 2021, an estimated 600 000 children were identified by Child Protective Services as experiencing abuse or neglect and an estimated 1820 children died of abuse and neglect.

Objective

The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of primary care–feasible or referable behavioral counseling interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of maltreatment.

Population

Children and adolescents younger than 18 years who do not have signs or symptoms of or known exposure to maltreatment.

Evidence Assessment

The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of primary care interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of or known exposure to maltreatment.

Recommendation

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement)
Using Effect Scores to Characterize Heterogeneity of Treatment Effects
Authors: Wang Guanbo , Heagerty Patrick J. , Dahabreh Issa J.
Published: March 2024

This JAMA Guide to Statistics and Methods article explains effect score analyses, an approach for evaluating the heterogeneity of treatment effects, and examines its use in a study of oxygen-saturation targets in critically ill patients.
Bacterial Infections
Authors: Wootton Catriona , Elliott Ivo
Published: March 2024

The skin provides a barrier between the body and the external environment and it is colonised by the bacteria and other microorganisms that make up the skin microbiome. Bacterial infections occur when bacteria invade through damage to the skin barrier, via trauma or pre‐existing skin conditions, or through inoculation or inhalation; bacterial skin infections can range from minor irritations to life‐threatening conditions. This chapter explores bacterial infections which can affect the skin, from the common to the rare, describing the epidemiology, presentation and management of each condition.
Mycobacterial Infections
Authors: Walker Stephen L. , Phillips Richard O.
Published: March 2024

The genus
Mycobacterium
contains more than 190 species of which over 25 are pathogenic in humans and other vertebrates. The most important obligate human pathogens are
M. tuberculosis
and
M. leprae
, but others such as
M. avium
complex (
M. avium
and
M. intracellulare
) and
M. ulcerans
are also significant. Disease‐causing mycobacteria other than those of the
M. tuberculosis
complex (including
M. tuberculosis
,
M. bovis
,
M. bovis
bacillus Calmette–Guérin (BCG) and related species) and
M. leprae
are referred to as non‐tuberculous mycobacteria (NTM), although the terms atypical, environmental or opportunistic mycobacteria are also used. This chapter will deal first with the general properties and characteristics of the mycobacteria, before discussing tuberculosis and highlighting aspects such as lupus vulgaris and tuberculids. Due to emergence and interest in NTMs, this section is substantially updated.
Syphilis and Congenital Syphilis
Authors: Kinghorn George R. , Omer Rasha
Published: March 2024

Bacterial sexually transmitted infections remain common causes of global ill health in which social, economic and behavioural factors are key determinants of their prevalence. They also have biological synergy with the human immunodeficiency virus. Although the incidence of early syphilis is again increasing in most high‐income countries, the classic late syndromes of ‘the great imitator’ causing premature death have become uncommon. Diagnostic techniques have continued to evolve. The World Health Organization has set ambitious targets for the eradication of congenital syphilis. Success requires coordinated multiagency approaches, enhanced surveillance efforts and reliability of appropriate penicillin supplies that have proved difficult to sustain in many low‐income countries.
Arthropods
Authors: Bernigaud Charlotte , Monsel Gentiane , Delaunay Pascal , Chosidow Olivier
Published: March 2024

This chapter provides an introductory overview of arthropods that are medically important to humans. The authors describe the anatomy and physiology of various arthropods, including insects, spiders and mites, and discuss their role in transmitting diseases to humans. They also provide guidance on identifying and managing arthropod bites, stings and infestations. The chapter includes information on the clinical presentation, diagnosis and management of common arthropod‐related conditions, such as lice, scabies and bed bug infestations. The authors emphasise the importance of a thorough patient history and physical examination in the diagnosis of arthropod‐related conditions, and provide practical advice on prevention and treatment. Overall, this chapter serves as a useful resource for medical doctors and dermatologists who encounter patients with arthropod‐related conditions in their practice.
Disorders Affecting Cutaneous Vasculature
Authors: Dompmartin Anne , Revencu Nicole , Boon Laurence M. , Vikkula Miikka
Published: March 2024

Disturbances can occur during the development of cutaneous vessels. These result in lesions that are called vascular anomalies. They are divided into vascular tumours and vascular malformations on the basis of clinical, radiological and histological aspects. Depending on the vessel type affected, the malformations are further divided into capillary, arteriovenous, venous and lymphatic malformations. The latter includes the group of variable primary lymphoedemas. Genetic testing is now added to the parameters used for diagnosis and classification. This has led to new group terms, such as PROS for PIK3CA‐related overgrowth syndromes and PIKopathies for vascular anomalies that have a mutation in the TIE2‐PI3K signalling pathway, as opposed to RASopathies with a mutation in the EPHB4‐RAS signalling pathway.
Dermatoses of Infancy
Authors: Solman Lea , Glover Mary T.
Published: March 2024

The term dermatoses of infancy covers a wide range of disorders, which are mainly encountered between the age of 4 weeks and 18 months. This chapter attempts to deal with the most common and important conditions that have not been covered in detail in other chapters.
Red/NIR‐I‐Fluorescence Carbon Dots Based on Rhein with Active Oxygen Scavenging and Colitis Targeting for UC Therapeutics
Authors: Xia Jiashan , Wang Jiayu , Liu Fengyuan , Chen Zhiqiong , Chen Changmei , Cheng Xiangshu , Chao Yu , Wang Yue , Deng Tao
Published: March 2024

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti‐inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability. L‐arginine, as a complement to NO, has synergistic and attenuating effects. In this paper, red/NIR‐I fluorescent carbon dots based on rhein and doped with L‐arginine (RA‐CDs), which are synthesized by a hydrothermal process without any organic solvents, are reported. RA‐CDs preserve a portion of the functional group of the active precursor, increase rhein solubility, and emit red/NIR‐I light for biological imaging. In vitro experiments show that RA‐CDs scavenge excessive reactive oxygen species (ROS), protect cells from oxidative stress, and enable the fluorescence imaging of inflamed colons. In a DSS‐induced UC mouse model, both delayed and prophylactic treatment with RA‐CDs via intraperitoneal and tail vein injections alleviate UC severity by reducing intestinal inflammation and restoring the intestinal barrier. This study highlights a novel strategy for treating and imaging UC with poorly soluble small‐molecule drugs.
MOF/MXene Composites: Synthesis, Application and Future Perspectives
Authors: Bibi Shumaila , Shah Syed Shoaib Ahmad , Nazir Muhammad Altaf , Helal Mohamed H. , El‐Bahy Salah M. , El‐Bahy Zeinhom M. , Ullah Sultan , Wattoo Muhammad Ahmad , Rehman Aziz ur
Published: March 2024

2D MXenes family creates an interest in environmental cleaning and energy conversion. It shows large surface functional groups, electronic transmission, and electrical conductivity. This research focuses on Metal Organic Framework‐based Ti3C2 heterojunctions, directing on surface morphology control, customizable electrical structure, high performance in Ti3C2‐based electrocatalytic devices, and energy storage as a supercapacitor. In addition, future development obstacles and viable research possibilities are presented. MXene detailed analysis reveals a fundamental study, structure‐activity connections, and potential research paths for environmental applications. Specially developed MOF/MXene nanoarchitectures with remarkable features are highlighted in several study fields, including the chemical sciences, environmental engineering, physics, catalysis, and nanotechnology. They represent a new class of cutting‐edge developing materials. Mainly, the presented review describes multiple synthesis approaches by adjusting conditions for MOF/MXene nanoarchitectures with varying morphologies, and intriguing properties can also be developed for electrochemical energy conversion and storage.
Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
Authors: Sánchez Julieta M. , López‐Laguna Hèctor , Parladé Eloi , Somma Angela Di , Livieri Andrea L. , Álamo Patricia , Mangues Ramón , Unzueta Ugutz , Villaverde Antonio , Vázquez Esther
Published: March 2024

Developing time‐sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non‐toxic microscale amyloid materials through the coordination between divalent metals and poly‐histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self‐disintegration process occurring in vitro and upon in vivo administration. Being these granules formed by a single pure protein species and therefore, chemically homogenous, they act as highly promising time‐sustained drug delivery systems. Despite their enormous clinical potential, the nature of the clustering process and the quality of the released protein have been so far neglected issues. By using diverse polypeptide species and their protein‐only oligomeric nanoscale versions as convenient models, a conformational rearrangement and a stabilization of the building blocks during their transit through the secretory granules, being the released material structurally distinguishable from the original source is proved here. This fact indicates a dynamic nature of secretory amyloids that act as conformational arrangers rather than as plain, inert protein‐recruiting/protein‐releasing granular depots.
Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR‐II Fluorescence Imaging
Authors: Zeng Fanwei , Li Changjian , Wang Han , Wang Yueqi , Ren Tingting , He Fangzhou , Jiang Jie , Xu Jiuhui , Wang Boyang , Wu Yifan , Yu Yiyang , Hu Zhenhua , Tian Jie , Wang Shidong , Tang Xiaodong
Published: March 2024

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen‐section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3‐IRDye800CW is synthesized by conjugating anti‐B7H3 antibody and IRDye800CW. B7H3‐IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor‐background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3‐IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin‐eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3‐IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.
Electrically Tunable Multiple‐Effects Synergistic and Boosted Photoelectric Performance in Te/WSe2 Mixed‐Dimensional Heterojunction Phototransistors
Authors: Cao Hechun , Hu Tao , Zhang Jiyue , Zhao Dongyang , Chen Yan , Wang Xudong , Yang Jing , Zhang Yuanyuan , Tang Xiaodong , Bai Wei , Shen Hong , Wang Jianlu , Chu Junhao
Published: March 2024

Mix‐dimensional heterojunctions (MDHJs) photodetectors (PDs) built from bulk and 2D materials are the research focus to develop hetero‐integrated and multifunctional optoelectronic sensor systems. However, it is still an open issue for achieving multiple effects synergistic characteristics to boost sensitivity and enrich the prospect in artificial bionic systems. Herein, electrically tunable Te/WSe2 MDHJs phototransistors are constructed, and an ultralow dark current below 0.1 pA and a large on/off rectification ratio of 106 is achieved. Photoconductive, photovoltaic, and photo‐thermoelectric conversions are simultaneously demonstrated by tuning the gate and bias. By these synergistic effects, responsivity and detectivity respectively reach 13.9 A W−1 and 1.37 × 1012 Jones with 400 times increment. The Te/WSe2 MDHJs PDs can function as artificial bionic visual systems due to the comparable response time to those of the human visual system and the presence of transient positive and negative response signals. This work offers an available strategy for intelligent optoelectronic devices with hetero‐integration and multifunctions.
Low Contact Resistance Organic Single‐Crystal Transistors with Band‐Like Transport Based on 2,6‐Bis‐Phenylethynyl‐Anthracene
Authors: Sun Yanan , Shi Xiaosong , Yu Yamin , Zhang Zhilei , Wu Miao , Rao Limei , Dong Yicai , Zhang Jing , Zou Ye , You Shengyong , Liu Jie , Lei Ming , Liu Chuan , Jiang Lang
Published: March 2024

Contact resistance has become one of the main bottlenecks that hinder further improvement of mobility and integration density of organic field‐effect transistors (OFETs). Much progress has been made in reducing contact resistance by modifying the electrode/semiconductor interface and decreasing the crystal thickness, however, the development of new organic semiconductor materials with low contact resistance still faces many challenges. Here, 2,6‐bis‐phenylethynyl‐anthracene (BPEA) is found, which is a material that combines high mobility with low contact resistance. Single‐crystal BEPA OFETs with a thickness of ≈20 nm demonstrated high mobility of 4.52 cm2 V−1 s−1, contact resistance as low as 335 Ω cm, and band‐like charge transport behavior. The calculated compatibility of the EHOMO of BPEA with the work function of the Au electrode, and the decreased |EHOMO‐ΦAu| with the increase of external electric field intensity from source to gate both contributed to the efficient charge injection and small contact resistance. More intriguingly, p‐type BPEA as a buffer layer can effectively reduce the contact resistance, improve the mobility, and meanwhile inhibit the double‐slope electrical behavior of p‐channel 2,6‐diphenyl anthracene (DPA) single‐crystal OFETs.
Ultrafast Metal‐Free Microsupercapacitor Arrays Directly Store Instantaneous High‐Voltage Electricity from Mechanical Energy Harvesters
Authors: Chen Shiqian , Li Zheng , Huang Po‐Han , Ruiz Virginia , Su Yingchun , Fu Yujie , Alesanco Yolanda , Malm B. Gunnar , Niklaus Frank , Li Jiantong
Published: March 2024

Harvesting renewable mechanical energy is envisioned as a promising and sustainable way for power generation. Many recent mechanical energy harvesters are able to produce instantaneous (pulsed) electricity with a high peak voltage of over 100 V. However, directly storing such irregular high‐voltage pulse electricity remains a great challenge. The use of extra power management components can boost storage efficiency but increase system complexity. Here utilizing the conducting polymer PEDOT:PSS, high‐rate metal‐free micro‐supercapacitor (MSC) arrays are successfully fabricated for direct high‐efficiency storage of high‐voltage pulse electricity. Within an area of 2.4 × 3.4 cm2 on various paper substrates, large‐scale MSC arrays (comprising up to 100 cells) can be printed to deliver a working voltage window of 160 V at an ultrahigh scan rate up to 30 V s−1. The ultrahigh rate capability enables the MSC arrays to quickly capture and efficiently store the high‐voltage (≈150 V) pulse electricity produced by a droplet‐based electricity generator at a high efficiency of 62%, significantly higher than that (<2%) of the batteries or capacitors demonstrated in the literature. Moreover, the compact and metal‐free features make these MSC arrays excellent candidates for sustainable high‐performance energy storage in self‐charging power systems.
Birth weight and nutritional status in school‐age children from Boane city, Mozambique
Authors: Malinga Eulálio , Leandro Carol Góis , de Almeida Araujo Fernanda Trigueiro , dos Santos Henrique Rafael , Tchamo Mario Eugénio , e Silva Wylla Tatiana Ferreira
Published: March 2024

Background

Birth weight is considered an important marker of inadequate maternal nutrition, and it is a critical indicator of the newborn's health and development.

Objective

This study evaluated the influence of low birth weight (LBW) on body composition in 7–10‐year‐old school children from Boane City—Mozambique.

Methods

A total of 220 children (female = 122 and male = 98) were divided into two groups according to their birth weight (LBW, n = 41; and normal birth weight, NBW, n = 179). Anthropometric indicators of nutritional status were analyzed by the indices weight‐for‐age, height‐for‐age, BMI‐for‐age, and weight‐for‐height.

Results

LBW children showed reduced skinfolds, and weight‐for‐height when compared to NBW children. Birth weight was positively associated with all anthropometric variables, except for BMI, which was not associated with any other variable. The r2 value ranged from .09 (weight‐for‐age) to .72 (height‐for‐age). For body composition variables, older children had higher fat mass (β = .26; 95% CI = 0.05–0.48) and fat‐free mass (β = 1.10; 95% CI = 0.71–1.48), and boys had lower fat percentage (β = −3.49; 95% CI = −4.35 to −2.65) and fat mass (β = −.92; 95% CI = −1.31 to −0.55) than girls. Birth weight was also positively associated with fat‐free mass.

Conclusion

LBW seems to influence some growth indicators of children living in Boane, however, current environmental factors seem to weaken this association. Our results suggest that public policies involving healthy nutrition and physical activity can reverse the effects of low weight in children from Boane.
Novel biallelic SASS6 variants associated with primary microcephaly and fetal growth restriction
Authors: Kong Xiangtian , Xu Jian , Yin Honggang , Jiang Hongru , Cao Xian , Cui Aimin , Wang Xueqian
Published: March 2024

Primary microcephaly is characterized by a head circumference prenatally or at birth that falls below three standard deviations from age‐, ethnic‐, and sex‐specific norms. Genetic defects are one of the underlying causes of primary microcephaly. Since 2014, five variants of the SASS6 gene have been identified as the cause of MCPH 14 in three reported families. In this study, we present the genetic findings of members of a nonconsanguineous Chinese couple with a history of microcephaly and fetal growth restriction (FGR) during their first pregnancy. Utilizing trio whole‐exome sequencing, we identified compound heterozygous variants involving a frameshift NM_194292.3:c.450_453del p.(Lys150AsnfsTer7) variant and a splice region NM_194292.3:c.1674+3A>G variant within the SASS6 gene in the affected fetus. Moreover, reverse transcriptase‐polymerase chain reaction from RNA of the mother's peripheral blood leukocytes revealed that the c.1674+3A>G variant led to the skipping of exon 14 and an inframe deletion. To the best of our knowledge, the association between FGR and SASS6‐related microcephaly has not been reported, and our findings confirm the pivotal role of SASS6 in microcephaly pathogenesis and reveal an expanded view of the phenotype and mutation spectrum associated with this gene.
Mitochondrial Dysfunction of Peripheral Platelets as a Predictive Biomarker for Postoperative Delirium in Elderly Patients
Authors: Yang Yan , Zhang Wei , Liu Yue , Liu Xin , Xie Jun , Xu Rui , Huang Yulin , Hao Jing , Sun Yu'e , Gu Xiaoping , Ma Zhengliang
Published: March 2024

Objective

To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients.

Methods

Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets.

Results

A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini‐Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini‐Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03–0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76–0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%.

Interpretation

Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024;96:74–86
Entschützende Funktionalisierung: eine direkte Umwandlung von Nms‐Amiden in Carbonsäureamide
Authors: Spieß Philipp , Brześkiewicz Jakub , Meyrelles Ricardo , Just David , Maulide Nuno
Published: March 2024

Klassische Schutzgruppenchemie erfordert unweigerlich einen Entschützungsschritt, um die ursprünglich blockierte Funktionalität vor weiteren Umwandlungen wiederherzustellen. Da dieser Aspekt der Schutzgruppenmanipulation zwangsläufig die Anzahl der Schritte jeder Synthesesequenz erhöht, bieten Methoden, die eine gleichzeitige Entschützung und Funktionalisierung ermöglichen („entschützende Funktionalisierung“, im Gegensatz zur Entschützung mit anschließender Funktionalisierung), attraktive Vorteile, um die Effizienz zu steigern und synthetische Routen zu verkürzen. In diesem Bericht präsentieren wir eine Methode zur entschützenden Funktionalisierung der neu eingeführten Nms‐Amide, die auf einer Analyse mittels Dichtefunktionaltheorie (DFT) basiert und die inhärente Nms‐Reaktivität ausnutzt. Mechanistische Studien erklären außerdem warum andere häufig verwendete Schutzgruppen nicht die gleichen Reaktivitätsmuster aufweisen. Die Anwendbarkeit dieses Ansatzes wurde anhand zahlreicher Substrate demonstriert und schließlich verwendet, um Arzneimittelderivate effizienter und mit verkürzten Synthesewegen herzustellen.
Non‐Heme Iron Enzymes Catalyze Heterobicyclic and Spirocyclic Isoquinolone Core Formation in Piperazine Alkaloid Biosynthesis
Authors: Pham Mai‐Truc , Yang Feng‐Ling , Liu I‐Chen , Liang Po‐Huang , Lin Hsiao‐Ching
Published: March 2024

We report the discovery and biosynthesis of new piperazine alkaloids‐arizonamides, and their derived compounds‐arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non‐heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3‐alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.
Umgehung von Ammoniak: Von N2 zu stickstoffhaltigen Heterocyclen ohne N1‐Zwischenprodukte oder Übergangsmetalle
Authors: Weber Marco , Kupfer Thomas , Arrowsmith Merle , Dewhurst Rian D. , Rang Maximilian , Ritschel Benedikt , Titlbach Sven , Ernst Martin , Rodrigues Marieli O. , da Silva Júnior Eufrânio N. , Braunschweig Holger
Published: March 2024

Diboradiazenverbindungen, die in einem Schritt aus einer Bor‐vermittelten Aktivierung von Distickstoff (N2) stammen, wurden separat mit Schwefel und Essigsäureanhydrid umgesetzt. Hierbei entstanden neuartige heterocyclische Verbindungen, die BN‐Isostere von Thiophen bzw. 1,3‐Oxazol sind. Diese einfachen Reaktionen stellen die letzten Schritte einer zweistufigen Syntheseroute zu komplexen Heterocyclen aus N2 dar, die sowohl auf den Einsatz an Übergangsmetallreagenzien verzichten als auch das klassische Zwischenprodukt Ammoniak vollständig umgehen.
Deprotective Functionalization: A Direct Conversion of Nms‐Amides to Carboxamides Using Carboxylic Acids
Authors: Spieß Philipp , Brześkiewicz Jakub , Meyrelles Ricardo , Just David , Maulide Nuno
Published: March 2024

The nature of protecting group chemistry necessitates a deprotection step to restore the initially blocked functionality prior to further transformation. As this aspect of protecting group manipulation inevitably adds to the step count of any synthetic sequence, the development of methods enabling simultaneous deprotection and functionalization (“deprotective functionalization”—distinct from “deprotection followed by functionalization”) is appealing, as it has the potential to improve efficiency and streamline synthetic routes. Herein, we report a deprotective functionalization of the newly introduced Nms‐amides guided by density functional theory (DFT) analysis, which exploits the inherent Nms reactivity. Mechanistic studies further substantiate and help rationalize the exquisite reactivity of Nms‐amides, as other commonly used protecting groups are shown not to exhibit the same reactivity patterns. The practicality of this approach was ultimately demonstrated in selected case studies.
Stable Anion Exchange Membrane Bearing Quinuclidinium for High‐performance Water Electrolysis
Authors: Yin Liqiang , Ren Rong , He Lanlan , Zheng Wentao , Guo Yu , Wang Linqin , Lee Husileng , Du Jian , Li Zhiheng , Tang Tang , Ding Guoheng , Sun Licheng
Published: March 2024

Anion exchange membranes (AEMs) are core components in anion exchange membrane water electrolyzers (AEM‐WEs). However, the stability of functional quaternary ammonium cations, especially under high temperatures and harsh alkaline conditions, seriously affects their performance and durability. Herein, we synthesized a 1‐methyl‐3,3‐diphenylquinuclidinium molecular building unit. Density functional theory (DFT) calculations and accelerated aging analysis indicated that the quinine ring structure was exceedingly stable, and the SN2 degradation mechanism dominated. Through acid‐catalyzed Friedel–Crafts polymerization, a series of branched poly(aryl‐quinuclidinium) (PAQ‐x) AEMs with controllable molecular weight and adjustable ion exchange capacity (IEC) were prepared. The stable quinine structure in PAQ‐x was verified and retained in the ex situ alkaline stability. Furthermore, the branched polymer structure reduces the swelling rate and water uptake to achieve a tradeoff between dimensional stability and ionic conductivity, significantly improving the membrane's overall performance. Importantly, PAQ‐5 was used in non‐noble metal‐based AEM‐WE, achieving a high current density of 8 A cm−2 at 2 V and excellent stability over 2446 h in a gradient constant current test. Based on the excellent alkaline stability of this diaryl‐quinuclidinium group, it can be further considered as a multifunctional building unit to create multi‐topological polymers for energy conversion devices used in alkaline environments.
Efficient self healable blended cationic and anionic poly(ionic liquids) under ambient conditions
Authors: Dhukia Surbhi , Singh Gaje , Singh Vinay , Singh Vasundhara
Published: March 2024

Poly(ionic liquid)‐based self‐healable electrolytes are getting tremendous attention owing to their quick self‐healing ability at ambient conditions without external stimulus, prominent safety, high mechanical strength, appreciably good conductivity, and no electrolyte leakage. Ionic interactions are much stronger and more dynamic, capable of imparting faster healing ability to the electrolyte. To exploit ionic interactions and non‐covalent hydrogen bonding simultaneously for faster self‐healing at ambient conditions. In the present work, free radical promoted copolymerization of 3‐methyl‐1‐vinylimidazolium iodide and sodium 4‐vinyl benzenesulfonate (VMeImI/SS) with poly(ethylene glycol) methyl ether acrylate and ureidopyrimidinone methacrylate to obtain cationic poly (PEG‐UPy‐Im) and anionic poly (PEG‐UPy‐SS) poly ionic liquid (PIL), respectively, as polymer electrolytes (PEs) have been achieved. The complete structural analysis of the copolymers by FTIR, 1H NMR, 13C NMR, DOSY‐NMR, and GPC was done. The ionic conductivity and self‐healing properties of the synthesized PEs, poly (PEG‐UPy‐Im) and poly (PEG‐UPy‐SS) were investigated, which gave encouraging results. For further enhancement of hydrogen bonding and ionic interactions, poly (PEG‐UPy‐Im) and poly (PEG‐UPy‐SS) were blended in the ratio of 1:1, referred to as poly (Im‐SS), a binary blend, as a self‐healable oppositely charged polyelectrolyte. Poly(Im‐SS) exhibited self‐healing behavior in 15 min and 5 min at 25 and 60°C, respectively, without any external stimulus. Poly(Im‐SS) also exhibited exceptionally high ionic conductivity of 2.04 × 10−5 and 11.48 × 10−5 Scm−1 at 30 and 80°C, respectively. This unique approach of blending two oppositely charged PEs to create a binary blend has improved ionic conductivity and self‐healing capabilities. Because a poly‐ionic network forms in poly(Im‐SS) as a binary blend, the physical and chemical properties in terms of mechanical and thermal stability as well as water contact angle point to a synergistic effect of ion–ion, ion–dipole, and quadruple Hbonding. Thus, the designed copolymer electrolytes and their blend, present a new perspective to develop innovative and rapid self‐healable polyelectrolytes with significant ionic conductivity for advanced electrochemical devices such as fuel cells, batteries, and supercapacitors.
Structural Insights on the Role of Halogen Bonding in Protein MEK Kinase‐Inhibitor Complexes
Authors: Milesi Pietro , Baldelli Bombelli Francesca , Lanfrancone Luisa , Gomila Rosa M. , Frontera Antonio , Metrangolo Pierangelo , Terraneo Giancarlo
Published: March 2024

Kinases are enzymes that play a critical role in governing essential biological processes. Due to their pivotal involvement in cancer cell signaling, they have become key targets in the development of anti‐cancer drugs. Among these drugs, those containing the 2,4‐dihalophenyl moiety demonstrated significant potential. Here we show how this moiety, particularly the 2‐fluoro‐4‐iodophenyl one, is crucial for the structural stability of the formed drug‐enzyme complexes. Crystallographic analysis of reported kinase‐inhibitor complex structures highlights the role of the halogen bonding that this moiety forms with specific residues of the kinase binding site. This interaction is not limited to FDA‐approved MEK inhibitors, but it is also relevant for other kinase inhibitors, indicating its broad relevance in the design of this class of drugs.
Legal apprenticeships: Enhancing capabilities, wellbeing, and diversity in the profession?
Authors: Casey Caroline , Mountford‐Zimdars Anna
Published: March 2024

This original study presents findings from a study of members of the first cohort of legal degree apprentices. Introduced in the UK in 2016, legal degree apprenticeships (LAs) remove uncertainty towards legal qualification in an otherwise competitive graduate recruitment environment and could help to increase social mobility into the professions. We examine the impact of the LA pathway on the development of wellbeing and capabilities of apprentices and traditional law students through the following research questions: does it enhance wellbeing when instead of loans, debt and insecurity, aspiring lawyers have a salary, no debt and secure job prospects through an apprenticeship pathway to qualification; and does using a capability framework offer a meaningful lens for understanding the experiences on different pathways? The analysis adopts a capabilities approach, intersected with an inequalities lens, to explore interviews with 23 aspiring solicitors, from different social backgrounds and at different stages of progression on the traditional university and LA pathways in England. The interviews explored access to and experiences of both pathways, particularly how participants were able to develop and convert their social and cultural resources into key capabilities. This provided a meaningful way to make sense of participants’ experiences. Capabilities were enhanced for LA students by removing stress and uncertainty around employment. This wellbeing gain was corroded for some by long commutes into work—often centred in London. Future quantitative research could establish whether, on balance, the majority of LA students experience an overall wellbeing gain. The capability framework usefully showed how across the LA and university pathways, all participants valued agency and developing all capabilities. Social capital was a key resource for creating opportunity and a desired capability that participants sought to develop.