bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Application of Robust Spiro [Fluorene‐9] CAAC Ruthenium Alkylidene Complexes for the “One‐Pot” Conversion of Allyl Acetate to Butane‐1,4‐diol
Authors: Erdélyi Ádám , Farkas Vajk , Turczel Gábor , Nagyházi Márton , Bényei Attila , Recta Merell Lystra Ledesma , Nagy Tibor , Kéki Sándor , Osterthun Ole , Klankermayer Jürgen , Tuba Róbert
Published: June 2024

A series of a novel CAAC ligands featuring a spiro‐fluorene group have been synthesized and complexed with ruthenium alkylidenes, yielding the corresponding Hoveyda‐type derivatives as a new family of olefin metathesis catalysts. The novel complexes have been characterized by XRD, HRMS and NMR measurements. The synthetised complexes were tested in catalysis and showed good activity in olefin metathesis, as demonstrated on diethyl diallylmalonate and allyl acetate substrates. The unique backbone in the ligand with the large, yet inflexible condensed system renders interesting properties to the catalyst, exemplified by the good catalytic performance and improved Z‐selectivity. In addition, the complex can also serve as a hydrogenation catalyst in a consecutive (one‐pot) reaction. The latter reaction can convert allyl acetate to butane‐1,4‐diol, a valuable chemical intermediate for biodegradable polybutylene succinate (PBS).
Ring Rearrangement Reactions of 4‐Alkenylisocoumarins and Photophysical Evaluation of Multi‐Substituted Anthracene Products
Authors: Kawazoe Teru , Yanai Hikaru , Fukuhara Toya , Kanatani Yusaku , Imakhlaf Amanda , Witulski Bernhard , Matsumoto Takashi
Published: June 2024

Herein we report that readily available 4‐alkenylisocoumarins can be regarded as potent dienolate equivalents. For example, lactol silyl ethers derived from 4‐alkenylisocoumarins were selectively converted to the corresponding benzo‐homophthalates through a fluoride‐induced ring opening step that was followed by a ring closure through a vinylogous intramolecular aldol condensation. Likewise, nucleophilic activation of 4‐alkenylisocoumarins directly yields diversely poly‐substituted naphthalenes and anthracenes without formation of any regioisomer. Photophysical evaluation of a set of thus obtained 1,3‐di‐ and 1,3,4‐trisubstituted anthracenes reveals their distinct intramolecular charge transfer (ICT) character during light absorption in polar solutions and excimer emission from the solid state when a face‐to‐face π‐stacked molecular assembly is present in the crystal packing.
Direct Inhibition of the YAP : TEAD Interaction: An Unprecedented Drug Discovery Challenge
Authors: Chène Patrick
Published: June 2024

The Hippo pathway, which is key in organ morphogenesis, is frequently deregulated in cancer. The TEAD (TEA domain family member) transcription factors are the most distal elements of this pathway, and their activity is regulated by proteins such as YAP (Yes‐associated protein). The identification of inhibitors of the YAP : TEAD interaction is one approach to develop novel anticancer drugs: the first clinical candidate (IAG933) preventing the association between these two proteins by direct competition has just been reported. The discovery of this molecule was particularly challenging because the interface between these two proteins is large (~3500 Å2 buried in complex formation) and made up of distinct contact areas. The most critical of these involves an omega‐loop (Ω‐loop), a secondary structure element rarely found in protein‐protein interactions. This review summarizes how the knowledge gained from structure‐function studies of the interaction between the Ω‐loop of YAP and TEAD was used to devise the strategy to identify potent low‐molecular weight compounds that show a pronounced anti‐tumor effect.
Intrinsic capacity and survival among older adults with gastrointestinal malignancies: The Cancer and Aging Resilience Evaluation registry
Authors: Maheshwari Supriya , Dai Chen , Giri Smith , Harmon Christian , Tucker Abigail , Fowler Mackenzie E. , Outlaw Darryl , Williams Grant R.
Published: June 2024

Background

Intrinsic capacity (IC) was introduced by the World Health Organization (WHO) as a marker of healthy aging, and is defined as the combination of an individual’s physical, mental, and psychological capacities. This study aimed to assess IC via a patient‐reported geriatric assessment (GA) and evaluate its association with survival among older adults with gastrointestinal (GI) malignancies.

Methods

Data were used from a single‐institution prospective registry of older adults undergoing GA before cancer therapy. Key domains of IC (vitality, locomotion, and sensory [hearing and visual], psychological, and cognitive capacities) were captured via GA, and each was given a score of 0 or 1 (0, impaired) to compute the total IC score (range, 0–6, where 6 indicates no impairment and ≤5 indicates impairment in ≥1 domains). A frailty index (FI) was measured via the deficit accumulation method. Cox regression models and Kaplan–Meier curves were used to examine the impact of IC impairment on survival.

Results

The study included 665 patients; the median age was 68 years, 57.4% were men, and 72.9% were White. The median IC score was 4, and 79.3% of participants showed impairment in ≥1 domains of IC. Most commonly impaired domains were locomotion (48.7%) and vitality (43.9%). IC was inversely associated with FI (Spearman coefficient, −0.75; p < .001). IC impairment was associated with inferior overall survival (score, 4–5: adjusted hazard ratio [aHR], 1.7; 95% CI, 1.11–2.48; score, 2–3: aHR, 1.9; 95% CI, 1.30–2.85; score, 0–1: aHR, 1.9; 95% CI, 1.11–2.48).

Conclusions

IC impairment is associated with frailty and reduced overall survival in older patients with GI malignancies. GA can be used to screen for IC impairment as recommended by the WHO.

Plain Language Summary

The World Health Organization introduced intrinsic capacity as a marker of healthy aging.

Intrinsic capacity is the combination of an individual’s physical, mental, and psychological capacities. It contains six key domains: vitality, locomotion, and sensory (hearing and visual), psychological, and cognitive capacities.

Older adults with cancer are susceptible to a decrease in intrinsic capacity as a result of cancer and the aging process.

In this study, we aimed to assess the intrinsic capacity for patients with gastrointestinal cancer and also identify whether there exists any association of intrinsic capacity with overall survival. We identified that approximately 80% of this population had one or more impaired domains, and more intrinsic capacity impairment was associated with reduced overall survival.
Recycling of iron and steel slag for carbon reduction and low‐environment load application
Authors: Xu Ying , Li Enshuo , Hu Chenguang , Zhang Fucheng , Meng Xianguang
Published: June 2024

The high‐value utilization of blast furnace slag (BFS) and steel slag (SS) as a valuable resource in the field of carbon reduction represents a green revolution, and also is an indispensable path toward breaking through resource and environmental constraints and achieving high‐quality, sustainable development through solid waste utilization in the steel industry. Achieving resource recycling while harnessing the untapped latent energy of resources and exploring their carbon sequestration capabilities has become a crucial avenue for further valorization through waste utilization. BFS and SS discharged from iron‐making or steel‐making furnaces carry a significant amount of latent heat, especially the calcium oxide component in SS, which gives it a unique advantage in the field of comprehensive BFS and SS utilization and carbonation‐based SS utilization. This article discusses the current research status of low‐carbon‐waste‐heat utilization in the production of microcrystalline glass, cementitious materials, functional adsorbents, and other products through front‐end modification of molten BFS and SS. This report also provides an overview of carbon capture by utilizing BFS and SS, offering insights into the research directions for subsequent heat recovery, online quality adjustment, high‐value utilization, and carbon sequestration using BFS and SS in the steel industry.
Population Pharmacokinetic and Exposure–Response Modeling to Inform Risankizumab Dose Selection in Patients With Ulcerative Colitis
Authors: Thakre Neha , Goebel Aline , Winzenborg Insa , Suleiman Ahmed A. , D'Cunha Ronilda , Mensing Sven , Liu Wei , Pang Yinuo
Published: June 2024

Data from phase IIb/III and phase III studies were used to characterize the population pharmacokinetics of risankizumab and its exposure–response relationships for efficacy and safety in ulcerative colitis (UC) patients. A two‐compartment model with first‐order absorption and elimination accurately described risankizumab pharmacokinetics. Although certain covariates, namely, body weight, serum albumin, fecal calprotectin, sex, corticosteroid use, advanced therapy inadequate response, and pancolitis, were statistically correlated with risankizumab clearance, their impact on exposure was not clinically meaningful for efficacy or safety. Phase II exposure–response analyses demonstrated that the 1,200 mg intravenous (IV) induction dose at Weeks 0, 4, and 8 achieved near maximal response for all efficacy end points, with suboptimal efficacy from the 600 mg and little added benefit from the 1,800 mg regimens, justifying 1,200 mg IV as the induction dose in the phase III study. Phase III exposure–response analyses for efficacy during induction showed statistically significant exposure–response relationships at Week 12 following 1,200 mg IV at Weeks 0, 4, and 8, in line with phase IIb results. Exposure–response analyses for maintenance demonstrated modest improvement in Week 52 efficacy when increasing the subcutaneous dose from 180 mg to 360 mg with largely overlapping confidence intervals. Exposure–response analyses for safety indicated no apparent exposure‐dependent safety events over the induction or maintenance treatment. Based on these results, the recommended dosing regimen for risankizumab in UC patients is 1,200 mg IV at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneously at Week 12 and every 8 weeks thereafter.
Nanopore‐Enabled Microbiome Analysis: Investigating Environmental and Host‐Associated Samples in Rainbow Trout Aquaculture
Authors: Zarantonello Giulia , Cuenca Argelia
Published: June 2024

Microbiome sequencing is at the forefront of health management development, and as such, it is becoming of great interest to monitor the microbiome in the aquaculture industry as well. Oxford Nanopore Technologies (ONT) platforms are gaining popularity to study microbial communities, enabling faster sequencing, extended read length, and therefore, improved taxonomic resolution. Despite this, there is a lack of clear guidelines to perform a metabarcoding study, especially when dealing with samples from non‐mammalian species, such as aquaculture‐related samples. In this article, we provide general guidelines for sampling, nucleic acid extraction, and ONT‐based library preparation for both environmental (water, sediment) and host‐associated (gill or skin mucus, skin, gut content, or gut mucosa) microbiome analysis. Our procedures focus specifically on rainbow trout (Oncorhynchus mykiss) reared in experimental facilities. However, these protocols can also be transferred to alternative types of samples, such as environmental DNA (eDNA) monitoring from alternative water sources, or to different fish species. The additional challenge posed by the low biomass and limited bacterial diversity inherent in fish‐associated microbiomes is addressed through the implementation of troubleshooting solutions. Furthermore, we describe a bioinformatic pipeline starting from raw reads and leading to taxonomic abundance tables using currently available tools and software. Finally, we provide a set of specific guidelines and considerations related to the strategic planning of a microbiome study within the context of aquaculture. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Environmental sample collection

Basic Protocol 2: Host‐associated sample collection

Alternate Protocol: Host‐associated sample collection: Alternative sample types

Basic Protocol 3: Sample pre‐treatment and nucleic acid extraction

Basic Protocol 4: Quality control and preparation for 16S rRNA gene sequencing

Support Protocol 1: Assessment of inhibition by quantitative PCR

Support Protocol 2: Bioinformatic analysis from raw files to taxonomic abundance tables
Efficient Photocatalytic Partial Oxidation of Aromatic Alcohols by Using ZnIn2S4 under Green Conditions.
Authors: Umair Muhammad , Pecoraro Claudio Maria , Di Franco Francesco , Santamaria Monica , Palmisano Leonardo , Loddo Vittorio , Bellardita Marianna
Published: June 2024

The ternary chalcogenide ZnIn2S4 (ZIS) has been synthesized by a simple hydrothermal method in which the carcinogen thiacetamide, universally used as a precursor, has been, for the first time, replaced successfully with the harmless thiourea. ZIS has been used as photocatalyst for the partial oxidation of different aromatic alcohols to their corresponding aldehyde in water solution, under ambient conditions and simulated solar light irradiation. The photocatalytic performance of ZnIn2S4 was better than TiO2 P25. In the presence of ZIS for 4‐methoxybenzyl alcohol, piperonyl alcohol, and benzyl alcohol, a selectivity towards the corresponding aldehyde of 99 % for a conversion of 46 %, 75 % for a conversion of 81 %, and 87 % for a conversion of 25 %, respectively, was obtained. For the same alcohols a selectivity of 19 % for a conversion of 41 %, 19 % for a conversion of 13 %, and 16 % for a conversion of 26 %, was observed in the presence of TiO2 P25.
Tailored Engineering of Layered Double Hydroxide Catalysts for Biomass Valorization: A Way Towards Waste to Wealth
Authors: Kumar Sahil , Choudhary Priyanka , Sharma Devendra , Sajwan Devanshu , Kumar Vinit , Krishnan Venkata
Published: June 2024

Layered double hydroxides (LDH) have significant attention in recent times due to their unique characteristic properties, including layered structure, variable compositions, tunable acidity and basicity, memory effect, and their ability to transform into various kinds of catalysts, which make them desirable for various types of catalytic applications, such as electrocatalysis, photocatalysis, and thermocatalysis. In addition, the upcycling of lignocellulose biomass and its derived compounds has emerged as a promising strategy for the synthesis of valuable products and fine chemicals. The current review focuses on recent advancements in LDH‐based catalysts for biomass conversion reactions. Specifically, this review highlights the structural features and advantages of LDH and LDH‐derived catalysts for biomass conversion reactions, followed by a detailed summary of the different synthesis methods and different strategies used to tailor their properties. Subsequently, LDH‐based catalysts for hydrogenation, oxidation, coupling, and isomerization reactions of biomass‐derived molecules are critically summarized in a very detailed manner. The review concludes with a discussion on future research directions in this field which anticipates that further exploration of LDH‐based catalysts and integration of cutting‐edge technologies into biomass conversion reactions hold promise for addressing future energy challenges, potentially leading to a carbon‐neutral or carbon‐positive future.
Arginine Acts as both Co‐solvent and Catalyst in Regioselective Eutectic‐Mediated Dimerization of Levulinic Acid
Authors: Neal Taylor , Dull Joseph , Barnabas Freddy , Bacca Lori , Thomas Jacqueline , Moore Curtis , Sun Yiping , Badjić Jovica
Published: June 2024

Invited for this issue's cover are Procter & Gamble's Corporate Analytical and Engineering Groups, along with the group of Professor Jovica Badjić and colleagues. The image, by Jennifer F. Neal, depicts the process of chemically upgrading the renewable, biomass‐derived levulinic acid by simplying mixing it with l‐arginine. The Research Article itself is available at 10.1002/cssc.202400503.
Dual‐port circularly polarized wideband dielectric resonator antenna for S‐band application
Authors: Gupta Vivek Kumar , Alam Monauwer , Sigroha Deepak , Yadav Abhimanyu , Sharma Anand
Published: June 2024

This article explains the design and implementation of a multiple input multiple output (two‐port) antenna, based on dielectric resonators. The antenna design not only demonstrates high isolation between its ports but also showcases robust diversity performance. The initial step introduces an asymmetrical ground plane radiating stub microstrip feed for circular polarization generation in a single‐port cylindrical dielectric resonator antenna (CDRA). This approach utilizes an asymmetrical ground plane and incorporates three radiating stubs connected to a microstrip feed line to generate HEM11δ modes in a cylindrical DRA. The proposed dual‐port CDRA offers high impedance bandwidth of 29.73% (2.95–3.98 GHz) and the axial ratio falls below 3 dB specifically from 3.01–3.35 GHz. The antenna demonstrates left‐handed circularly polarized fields with an average gain of 4.95 dBi and a radiation efficiency of 90.56%. All of these characteristics make the developed radiator appropriate for WiMAX (3.3–3.5 GHz) applications.
Overall and cause‐specific mortality in anorexia nervosa; impact of psychiatric comorbidity and sex in a 40‐year follow‐up study
Authors: Søeby Mette , Gribsholt Sigrid Bjerge , Clausen Loa , Richelsen Bjørn
Published: June 2024

Objective

This study investigates the overall and cause‐specific mortality in males and females with anorexia nervosa (AN) from 1977 to 2018, focusing on the impact of psychiatric comorbidity on mortality risk, a less explored aspect despite a high prevalence in patients with AN.

Method

We conducted a nationwide population‐based cohort study in Denmark including all patients with AN (n = 14,774) with a median follow‐up time of 9.1 years and a 1:10 age‐ and sex‐matched general population comparison cohort. Using Cox proportional hazard model, we calculated adjusted hazard ratios (aHR) for death stratified by psychiatric comorbidity, sex, and age at AN onset and evaluated the causes of death using Fine and Gray sub‐distribution hazard ratios (SHR).

Results

In patients with AN, the weighted average aHR for all‐cause mortality was 4.5 [95% CI 4.1–4.9] with up to 40 years follow‐up. Psychiatric comorbidity was present in 47% of patients with AN at index date, which was associated with a 1.9‐fold increase in 10‐year mortality compared with patients without comorbidity and a notably four‐fold increase, when diagnosed at age 6–25 years. The mortality risk was similar according to sex. 13.9% of all deaths in patients with AN were due to suicide (SHR 10.7 [8.1–14.2]). The risk of dying of natural causes was increased with a SHR of 3.8 [95% CI 3.4–4.2].

Discussion

The increased mortality risk in both males and females with AN and psychiatric comorbidity, particularly when diagnosed at young age, underscores the need for comprehensive treatment addressing both AN and coexisting psychiatric conditions.

Public Significance

The mortality in patients with anorexia nervosa (AN) is high and we show in our study that the mortality is doubled in the presence of psychiatric comorbidity particularly the first 10 years after diagnosis seen in both sexes and with suicide as a major cause of death. These findings stress the importance of detection and treatment of psychiatric comorbidities alongside the eating disorder to prevent fatal outcome.
Precision integration of uniform molecular‐level carbon into porous silica framework for synergistic electrochemical activation in high‐performance lithium–ion batteries
Authors: Oh Seungbae , Dong Xue , Woo Chaeheon , Zhang Xiaojie , Kim Yeongjin , Choi Kyung Hwan , Lee Bom , Kim Ji‐Hee , Kang Jinsu , Bang Hyeon‐Seok , Jeon Jiho , Oh Hyung‐Suk , Yu Hak Ki , Mun Junyoung , Choi Jae‐Young
Published: June 2024

The development of advanced anode materials for lithium‐ion batteries that can provide high specific capacity and stable cycle performance is of paramount importance. This study presents a novel approach for synthesizing molecular‐level homogeneous carbon integration to porous SiO2 nanoparticles (SiO2@C NPs) tailored to enhance their electrochemical activities for lithium‐ion battery anode. By varying the ratio of the precursors for sol–gel reaction of (phenyltrimethoxysilane (PTMS) and tetraethoxysilane (TEOS)), the carbon content and porosity within SiO2@C NPs is precisely controlled. With a 4:6 PTMS and TEOS ratio, the SiO2@C NPs exhibit a highly mesoporous structure with thin carbon and the partially reduced SiOx phases, which balances ion and charge transfer for electrochemical activation of SiO2@C NPs resulting remarkable capacity and cycle performance. This study offers a novel strategy for preparing affordable high capacity SiO2‐based advanced anode materials with enhanced electrochemical performances.

image
Timing of postoperative radiation therapy for major salivary gland cancers
Authors: Yan Flora , Liu Jeffrey C. , Shulman Rebecca , Galloway Thomas J. , Ridge John A. , Yao Christopher M. K. L.
Published: June 2024

Background

The impact of timing of PORT initiation for major salivary gland cancers on survival is unknown. We aim to examine the impact of PORT timeliness on overall survival (OS) of patients with major salivary gland cancers.

Methods

This was a cross‐sectional analysis using data from the National Cancer Database (2004–2017) and included patients with major salivary gland cancer treated with surgery and PORT.

Results

In total, 5701 patients were included (3133 [55%] male, 4644 [82%] white, mean age 59 ± 16 years). For the overall cohort, PORT >6 weeks was not associated with decreased OS (1.00 aHR, 95% CI 0.89–1.11). When specifically examining patients with mucoepidermoid carcinoma, PORT >6 weeks was associated with a decreased OS (1.27 aHR, 95% CI 1.01–1.58).

Conclusions

Overall, this analysis did not demonstrate a survival benefit for initiating PORT within 6 weeks for patients with salivary gland malignancies. Subset analysis did support initiating PORT within 6 weeks after resection for patients with mucoepidermoid carcinomas. This was not demonstrated in other major salivary gland cancer histologies.
Myrrh sitz bath for wound healing after hemorrhoidectomy: A retrospective study of adverse effects and treatment outcomes
Authors: Al Amri Fahad Saeed
Published: June 2024

Background and Aim

Hemorrhoids affect 75% of people worldwide. surgical hemorrhoidectomy remains the definitive intervention for severe cases. Postoperative wound care is critical, and alternative treatments, like Myrrh, are of growing interest due to their potential wound‐healing properties. This study aimed to compare the safety, efficacy, and treatment outcomes of Myrrh sitz baths with standard clinical care in promoting wound healing after hemorrhoidectomy.

Methods

A retrospective cohort study was carried out using medical records from Abha Private Hospital for the period of January–December 2022. The data of patients who underwent hemorrhoidectomy were collected and categorized based on postoperative wound care into two groups: Group A for Myrrh‐based wound care as a self‐medication and Group B for standard wound care.

Results

The study included 67 patients who underwent hemorrhoidectomy. Out of these patients, 52 had standard wound care, while 15 used Myrrh‐based wound care as self‐treatment without medical advice. The Myrrh group patients were significantly older with more comorbidities. The Myrrh group had significant Grade III wound healing outcomes 9/15 (60%) compared to the standard care group 2/52 (3.8%) (p < 0.001). However, despite the better healing outcomes, the Myrrh group had a significantly higher complication rate 7/15(46.7%) than the standard care group 1/52 (1.9%) (p < 0.001). These results indicate that despite the good healing capacity of Myrrh, cautious usage must be considered.

Conclusion

Myrrh sitz baths appear more effective than standard wound care in enhancing healing after hemorrhoidectomy. However, increased complications suggest the necessity for comprehensive evaluation and research on its safety profile. These findings can guide future research and clinical practices related to postoperative wound care.
The Great Codon Escape: Vacating Codons for Genetic Code Expansion and Ribosome Stalling
Authors: Hopstaken Antonius J. P. , Große Wichtrup Enno , Jongkees Seino A. K.
Published: June 2024

In ribosomal synthesis of peptides and proteins, genetic information is translated into an amino acid polymer according to the genetic code, which describes the translational command encoded by each codon. However, parts of the genetic code can be adjusted to customize translations. One option is to remove decoding for a specific codon, resulting in a vacant codon. Such vacant codons can be used to stall the ribosome for mechanistic studies and display techniques. Alternatively, the liberated codon can be assigned to encode for incorporation of a noncanonical building block for expansion of the genetic code. In this review we provide an overview of the methods currently available for vacating codons in prokaryotic translation (agnostic of how these are later applied), targeting factors such as amino‐acyl tRNA synthetases, tRNA, release factors, and the initiation machinery. Moreover, we assess applicability and compatibility of the currently available techniques and discuss which have the potential to develop into even more powerful approaches in the future.
First‐trimester fasting plasma glucose levels and progression to type 2 diabetes: A 5‐year cohort study
Authors: Maor‐Sagie Esther , Hallak Mordechai , Twig Gilad , Toledano Yoel , Gabbay‐Benziv Rinat
Published: June 2024

Objective

Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100–125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first‐trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first‐ trimester fasting plasma glucose levels, as compared with gestational diabetes, a well‐established risk factor for diabetes, in up to 5‐year follow‐up postpartum.

Methods

A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post‐delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic‐area under the curve (ROC‐AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status.

Results

The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut‐off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity.

Conclusions

Increased first‐trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first‐trimester fasting plasma glucose has a more pronounced impact on progression to diabetes.
Isotretinoin‐associated intracranial hypertension: A concise report
Authors: Vashisht Kanya Rani , Varma Sachin , Yeganegi Mahtab
Published: June 2024

We present a case of a 24‐year‐old preobese female undergoing isotretinoin treatment for acne vulgaris, who experienced drug‐induced intracranial hypertension (DIIH). Recognizing and addressing this potentially serious adverse effect is essential to prevent severe outcomes, particularly irreversible vision impairment. When suspected, immediate discontinuation of isotretinoin, neuroradiological imaging and urgent ophthalmologic evaluation to rule out papilloedema is imperative. Formulation of alternative treatment strategies, caution while prescribing DIIH‐causing drugs in future patient treatments and proactive reporting of adverse events are integral aspects of its comprehensive management.
Better operating room efficiency and reduced staff demand: Individualised versus off‐the‐shelf total knee arthroplasty
Authors: Sappey‐Marinier Elliot , Beel Wouter ,   ReSurg, Bonnin Michel P. , Aït‐Si‐Selmi Tarik
Published: June 2024

Purpose

The purpose of this pilot cross‐sectional study was to compare the operating room (OR) efficiency and intraoperative staff task load when performing individualised versus off‐the‐shelf (OTS) total knee arthroplasty (TKA).

Methods

A consecutive series of 28 patients randomised (1:1) to receive either OTS TKA or individualised TKA were included. The OR staff workload was assessed with the NASA Task Load Index (TLX), a subjective grading system assessing mental demand, physical demand, temporal demand, performance, effort and frustration on a scale from 0 (very low) to 20 (very high). The time for patient preparation, surgical time, closure and total OR time was recorded to assess OR efficiency. Effect sizes of differences between OTS and individualised TKA were expressed as mean differences (MDs) with 95% confidence intervals (CIs).

Results

Patients in both cohorts were similar in age (OTS vs. individualised TKA (median [IQR]), 67 [63–76] vs. 71 [68–79]; p = 0.207) and body mass index (BMI) (29 [24–33] vs. 29 [26–31]; p = 0.807), and there were no significant differences in other preoperative characteristics. The OR staff perceived individualised TKA as less demanding than OTS TKA: Individualised TKA was rated significantly better across the six domains of the NASA TLX: mental demand by 5.6 points, physical demand by 6.3 points, temporal demand by 5.3 points, performance by 3.6 points, effort by 5.9 points and frustration by 5.8 points. Individualised TKA resulted in statistically significantly shorter mean total OR time (MD, 10 min; p = 0.018).

Conclusion

The staff in the OR found that individualised TKA is less mentally, physically and temporally demanding than OTS TKA. The average total time spent in the OR during individualised TKA is 10 min less than during OTS TKA.

Clinical Trial Registration

This study constitutes a part of a larger registered randomised controlled trial comparing patient satisfaction following OTS versus individualised TKA (NCT04460989).

Level of Evidence

Level III.
Bidirectional needs assessment of otolaryngology–head and neck surgery short‐term surgical trips in Zimbabwe
Authors: Green Katerina J. , Matinhira Naboth , Jain Amiti , Arya Priya , Douse Dontre' M. , Dzongodza Titus , Chidziva Clemence , Wiedermann Joshua P.
Published: June 2024

Objectives

To describe findings from an otolaryngology‐specific needs assessment tool in Zimbabwe.

Methods

Surveys were developed and shared with Low‐Middle Income Country (LMIC) hosting institutions in Zimbabwe and to High‐Income Country surgical trip participants (HIC). Respondents were otolaryngologists identified online and through professional networks who had participated in a surgical trip.

Results

The most common procedures Zimbabwe otolaryngologists reported treating were adenotonsillectomy (85.7%), chronic rhinosinusitis (71.4%), chronic otitis (57.1%), and head and neck tumor intervention (57.1%). The most common untreatable conditions that host physicians wanted to treat were skull base surgery (71.4%), flap reconstructions (57.1%), and laryngotracheal reconstruction (57.1%). The largest discrepancy between host desires and visiting team offerings were flap reconstruction (57.1%), nasal bone deformities (37.1%), and laryngotracheal reconstruction (17.1%). Perceptions of short‐term surgical trips (STST) were recorded for host and visiting teams, and important differences between the public and private sectors of care in Zimbabwe were also identified.

Conclusion

The surveys utilized in this study served as a bidirectional needs assessment of the requirements and care goals of host institutions and visiting teams in Zimbabwe. Differences between public and private sectors of care, particularly regarding infrastructure, resources, and surgical goals, were revealed, and the results can be utilized as part of efforts to maximize efforts within global surgical partnerships.

Level of Evidence

VI.
Molecular and transcriptional basis of bidirectional CD4+ T cell exhaustion in oropharyngeal squamous cell carcinoma
Authors: Cheng Danni , Qiu Ke , Li Daibo , Mao Minzi , Rao Yufang , Song Yao , Feng Lan , Shao Xiuli , Jiang Chuanhuan , Wang Yan , Li Li , Chen Xuemei , Wu Sisi , Wang Haiyang , Liu Jun , Yu Haopeng , Zhang Wei , Chen Fei , Zhao Yu , Ren Jianjun
Published: June 2024

Tumor‐infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion‐related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune‐promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor‐infiltrating CD4+ T cells were identified, and both the immune‐promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD‐1) and Treg cells in Module 2 (αCTLA‐4) in mouse models could help reinvigorate the effector function of Module 1‐exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2‐exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.
Robin coefficient determination problem in a fractional parabolic differential equation
Authors: Sidi Maawiya Ould , Sidi Hamed Ould , Alosaimi Moataz , Mahmoud Sid Ahmed Ould Ahmed , Beinane Sid Ahmed Ould , Alshammari Hadi Obaid
Published: June 2024

This article discusses the identification of an unknown Robin coefficient in a fractional parabolic equation using a noisy measurement of the ultimate solution over time. The problem is quite complex, involving a nonlocal, nonlinear, and ill‐posed operator. To solve this problem, the article proposes a regularized optimization approach that minimizes a least‐squares cost function. The article also examines the various conceptual and real‐world challenges associated with this problem. The article demonstrates the presence of a singular and stable solution for the optimization problem. It utilizes the Morozov discrepancy principle and the conjugate gradient method to streamline the iterative reconstruction process. The proposed method is accurate and efficient, as several numerical examples demonstrate.
Hyperglycemia Inhibits Hepatic SHBG Synthesis Through the NGBR‐AMPK‐HNF4 Pathway in Rats with Polycystic Ovary Syndrome Induced by Letrozole in Combination with a High‐Fat Diet
Authors: Hu Rao , Long Shuanglian , Luo Min , Tang Bowen , Tan Tao , Dong Weilei , Wang Qian , Zhang Jiaming
Published: June 2024

Scope

Polycystic ovary syndrome (PCOS) is closely related to non‐alcoholic fatty liver disease (NAFLD), and sex hormone‐binding globulin (SHBG) is a glycoprotein produced by the liver. Hepatic lipogenesis inhibits hepatic SHBG synthesis, which leads to hyperandrogenemia and ovarian dysfunction in PCOS. Therefore, this study aims to characterize the mechanism whereby liver lipogenesis inhibits SHBG synthesis.

Methods and results

This study establishes a rat model of PCOS complicated by NAFLD using a high‐fat diet in combination with letrozole and performs transcriptomic analysis of the liver. Transcriptomic analysis of the liver shows that the expression of neurite growth inhibitor‐B receptor (NgBR), hepatocyte nuclear factor 4α (HNF4α), and SHBG is low. Meantime, HepG2 cells are treated with palmitic acid (PA) to model NAFLD in vitro, which causes decreases in the expression of NgBR, HNF4α, and SHBG. However, the expression of HNF4α and SHBG is restored by treatment with the AMP‐activated protein kinase (AMPK) agonist AICAR.

Conclusions

NgBR regulates the expression of HNF4α by activating the AMPK signaling pathway, thereby affecting the synthesis of SHBG in the liver. Further mechanistic studies regarding the effect of liver fat on NGBR expression are warranted.
Determination of Veratrum alkaloid contents in three Veratrum species by HPLC‐MS/MS
Authors: Siegle Julia , Pietsch Jörg
Published: June 2024

Introduction

Veratrum alkaloids have gained attention due to their toxic effects and potential pharmaceutical applications, particularly in cancer and cardiology. Over 200 alkaloids are found in species of the Veratrum genus. The alkaloid composition and concentrations can greatly vary in plants depending on factors like species, plant part, location, season, weather, or nutrients.

Objective

This study aims an analytical approach to analyze and quantify Veratrum alkaloids in different plant parts of Veratrum species. The purpose is to contribute essential alkaloid concentration data for future research on the pharmacological and toxicological aspects of Veratrum alkaloids.

Methods

This study focuses on five Veratrum alkaloids (cevadine, jervine, protoveratrine A, veratramine, and veratridine) in three Veratrum species (Veratrum album L., Veratrum californicum Durand, and Veratrum nigrum L.) collected from four German botanical gardens (Dresden, Leipzig, Marburg, and Schellerhau). A liquid–liquid extraction method and a sensitive high‐performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS) method operating in multiple reaction monitoring (MRM) mode were applied for the alkaloid determination.

Results

Quantification revealed varying alkaloid concentrations among plant parts and Veratrum species in the μg/g to mg/g range. Protoveratrine A exhibited the highest content, while veratramine concentrations were generally lower. Especially in fruit, roots and rootstock of Veratrum album L. alkaloid concentrations were significant high.

Conclusion

The developed HPLC‐MS/MS method successfully determined Veratrum alkaloid concentrations in plant samples. The study contributes valuable data on Veratrum alkaloid distribution in different species and plant parts, crucial for understanding their potential medicinal and toxicological significance.
Prenatal exome sequencing for morphologically normal fetus: Should we be doing it?
Authors: Gao Zhi , Zhu Xiaofan , Ren Huanan , Wang Yanfei , Hua Chunxiao , Kong Xiangdong
Published: June 2024

Objective

We aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses.

Method

This retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023.

Results

Overall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at risk of having a future pregnancy with a recessive condition. Among the six fetuses detected with monogenic disorders, two fetuses carried a de novo variant in OPA1 and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis, respectively. One fetus was detected with a maternally inherited variant in PKD2 related to polycystic kidney disease 2 (not known to the mother until then). One fetus was detected with a maternally inherited variant in SDHB associated with Pheochromocytoma. Two fetuses carried compound heterozygous variants in NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness, respectively. In the 2 families where parents were found to be carriers but the fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes were detected in the parents, respectively, which are associated with deafness and palmoplantar keratoderma.

Conclusion

Our research indicated that pES can provide significant critical information for families with morphologically normal fetuses. Prenatal screening with exome sequencing requires careful management and detailed pre‐test and post‐test genetic counseling.
“Let's keep calm and breathe”—A mindfulness meditation program in school and its effects on children's behavior and emotional awareness: An Australian pilot study
Authors: Stapleton Peta , Dispenza Joseph , Douglas Angela , Dao Van , Kewin Sarah , Le Sech Kyra , Vasudevan Anitha
Published: June 2024

This study aimed to understand how mindfulness meditation affects young people by examining its impact on self‐regulation, happiness, emotional awareness, and school performance among two groups of school children. A 10‐week mindfulness program was conducted by a meditation expert for 552 children aged 4–8 (Group 1) and 287 children aged 9–11 (Group 2). Results for the 4–8 years group (Group 1) showed meditation predicted an increase in happiness (R2 = .003, p < .001) and self‐reported school performance (R2 = .005, p < .001) and a decrease in emotional (R2 = .017, p < .001) and behavioral difficulties (R2 = .009, p < .001); however, the effect sizes were small. In the 9–11 years group (Group 2), meditation predicted an increase in emotional awareness (R2 = .02, p < .001), and a decrease in emotional (R2 = .014, p < .001) and behavioral difficulties (R2 = .009, p < .001) as measured by scores from baseline to postintervention. For Group 2, there was no significant change in happiness over the 10 weeks. The findings support incorporating mindfulness meditation in schools, noting significant enhancements in self‐regulation with just 5 min of daily practice.
The effects of combining repetitive transcranial magnetic stimulation with task‐specific training on gait performance in individuals with Parkinson's disease: A review article
Authors: Niemrungruang Kanjana , Thanakamchokchai Jenjira , Pongmala Chatkaew , Khobkhun Fuengfa
Published: June 2024

Background

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments, especially in the area of gait disturbances. Physiotherapy, with a focus on task‐specific training, has demonstrated a level of efficacy as regards alleviating symptoms and enhancing functional capabilities in individuals with PD. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a potential therapeutic intervention for improving motor functions in individuals with PD.

Aims

This review article aims to investigate the effects of combining rTMS with task‐specific training on gait performance in individuals with PD.

Materials and Methods

PubMed, Physiotherapy Evidence Database (PEDro), and Scopus were all searched for relevant studies. The focus of the search was on studies that investigated the efficacy of combining rTMS with task‐specific training to improve gait performance in individuals with PD.

Results

Four studies were identified as fulfilling the eligibility criteria and were included in the study. The combination of rTMS with specific treadmill training and weight‐bearing exercises can significantly enhance walking efficiency, including improvements in walking speed, self‐mobility, and step rate. In addition, the combination of rTMS and task‐specific training, such as treadmill‐based training, shows promise in enhancing gait performance in individuals with PD.

Discussion and Conclusion

High‐frequency rTMS targeting the primary motor cortex (or M1) can result in improved walking speed, self‐mobility, and step rate. However, limited research exists regarding low‐frequency stimulation of the supplementary motor area (SMA) in individuals with gait issues. Further research is required to determine the optimal parameters of rTMS, such as strength, frequency, and duration of stimulation and it is worth considering the incorporation of additional training modalities, including cognitive exercises.
Lytic transglycosylase Slt of Pseudomonas aeruginosa as a periplasmic hub protein
Authors: Avila‐Cobian Luis F. , De Benedetti Stefania , Hoshino Hidekazu , Nguyen Van T. , El‐Araby Amr M. , Sader Safaa , Hu Daniel D. , Cole Sara L. , Kim Choon , Fisher Jed F. , Champion Matthew M. , Mobashery Shahriar
Published: June 2024

Peptidoglycan is a major constituent of the bacterial cell wall. Its integrity as a polymeric edifice is critical for bacterial survival and, as such, it is a preeminent target for antibiotics. The peptidoglycan is a dynamic crosslinked polymer that undergoes constant biosynthesis and turnover. The soluble lytic transglycosylase (Slt) of Pseudomonas aeruginosa is a periplasmic enzyme involved in this dynamic turnover. Using amber‐codon‐suppression methodology in live bacteria, we incorporated a fluorescent chromophore into the structure of Slt. Fluorescent microscopy shows that Slt populates the length of the periplasmic space and concentrates at the sites of septation in daughter cells. This concentration persists after separation of the cells. Amber‐codon‐suppression methodology was also used to incorporate a photoaffinity amino acid for the capture of partner proteins. Mass‐spectrometry‐based proteomics identified 12 partners for Slt in vivo. These proteomics experiments were complemented with in vitro pulldown analyses. Twenty additional partners were identified. We cloned the genes and purified to homogeneity 22 identified partners. Biophysical characterization confirmed all as bona fide Slt binders. The identities of the protein partners of Slt span disparate periplasmic protein families, inclusive of several proteins known to be present in the divisome. Notable periplasmic partners (KD < 0.5 μM) include PBPs (PBP1a, KD = 0.07 μM; PBP5 = 0.4 μM); other lytic transglycosylases (SltB2, KD = 0.09 μM; RlpA, KD = 0.4 μM); a type VI secretion system effector (Tse5, KD = 0.3 μM); and a regulatory protease for alginate biosynthesis (AlgO, KD < 0.4 μM). In light of the functional breadth of its interactome, Slt is conceptualized as a hub protein within the periplasm.