bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic sequence engineering enhances the induction strength of the glucose-regulated GTH1 promoter of Komagataella phaffii
Authors: Flores-Villegas Mirelle , Rebnegger Corinna , Kowarz Viktoria , Prielhofer Roland , Mattanovich Diethard , Gasser Brigitte
Published: October 2023

The promoter of the high-affinity glucose transporter Gth1 (PGTH1) is tightly repressed on glucose and glycerol surplus, and strongly induced in glucose-limitation, thus enabling regulated methanol-free production processes in the yeast production host Komagataella phaffii. To further improve this promoter, an intertwined approach of nucleotide diversification through random and rational engineering was pursued. Random mutagenesis and fluorescence activated cell sorting of PGTH1 yielded five variants with enhanced induction strength. Reverse engineering of individual point mutations found in the improved variants identified two single point mutations with synergistic action. Sequential deletions revealed the key promoter segments for induction and repression properties, respectively. Combination of the single point mutations and the amplification of key promoter segments led to a library of novel promoter variants with up to 3-fold higher activity. Unexpectedly, the effect of gaining or losing a certain transcription factor binding site (TFBS) was highly dependent on its context within the promoter. Finally, the applicability of the novel promoter variants for biotechnological production was proven for the secretion of different recombinant model proteins in fed batch cultivation, where they clearly outperformed their ancestors. In addition to advancing the toolbox for recombinant protein production and metabolic engineering of K. phaffii, we discovered single nucleotide positions and correspondingly affected TFBS that distinguish between glycerol- and glucose-mediated repression of the native promoter.
Development of a novel tobramycin dependent riboswitch
Authors: Kraus Leon , Duchardt-Ferner Elke , Bräuchle Eric , Fürbacher Simon , Kelvin Daniel , Marx Hans , Boussebayle Adrien , Maurer Lisa-Marie , Bofill-Bosch Cristina , Wöhnert Jens , Suess Beatrix
Published: October 2023

We herein report the selection and characterization of a new riboswitch dependent on the aminoglycoside tobramycin. Its dynamic range rivals even the tetracycline dependent riboswitch to be the current best performing, synthetic riboswitch that controls translation initiation. The riboswitch was selected with RNA Capture-SELEX, a method that not only selects for binding but also for structural changes in aptamers on binding. This study demonstrates how this method can fundamentally reduce the labour required for the de novo identification of synthetic riboswitches. The initially selected riboswitch candidate harbours two distinct tobramycin binding sites with KDs of 1.1 nM and 2.4 μM, respectively, and can distinguish between tobramycin and the closely related compounds kanamycin A and B. Using detailed genetic and biochemical analyses and 1H NMR spectroscopy, the proposed secondary structure of the riboswitch was verified and the tobramycin binding sites were characterized. The two binding sites were found to be essentially non-overlapping, allowing for a separate investigation of their contribution to the activity of the riboswitch. We thereby found that only the high-affinity binding site was responsible for regulatory activity, which allowed us to engineer a riboswitch from only this site with a minimal sequence size of 33 nt and outstanding performance.
scQTLbase: an integrated human single-cell eQTL database
Authors: Ding Ruofan , Wang Qixuan , Gong Lihai , Zhang Ting , Zou Xudong , Xiong Kewei , Liao Qi , Plass Mireya , Li Lei
Published: October 2023

Genome-wide association studies (GWAS) have identified numerous genetic variants associated with diseases and traits. However, the functional interpretation of these variants remains challenging. Expression quantitative trait loci (eQTLs) have been widely used to identify mutations linked to disease, yet they explain only 20–50% of disease-related variants. Single-cell eQTLs (sc-eQTLs) studies provide an immense opportunity to identify new disease risk genes with expanded eQTL scales and transcriptional regulation at a much finer resolution. However, there is no comprehensive database dedicated to single-cell eQTLs that users can use to search, analyse and visualize them. Therefore, we developed the scQTLbase (http://bioinfo.szbl.ac.cn/scQTLbase), the first integrated human sc-eQTLs portal, featuring 304 datasets spanning 57 cell types and 95 cell states. It contains ∼16 million SNPs significantly associated with cell-type/state gene expression and ∼0.69 million disease-associated sc-eQTLs from 3 333 traits/diseases. In addition, scQTLbase offers sc-eQTL search, gene expression visualization in UMAP plots, a genome browser, and colocalization visualization based on the GWAS dataset of interest. scQTLbase provides a one-stop portal for sc-eQTLs that will significantly advance the discovery of disease susceptibility genes.
MultifacetedProtDB: a database of human proteins with multiple functions
Authors: Bertolini Elisa , Babbi Giulia , Savojardo Castrense , Martelli Pier Luigi , Casadio Rita
Published: October 2023

MultifacetedProtDB is a database of multifunctional human proteins deriving information from other databases, including UniProt, GeneCards, Human Protein Atlas (HPA), Human Phenotype Ontology (HPO) and MONDO. It collects under the label ‘multifaceted’ multitasking proteins addressed in literature as pleiotropic, multidomain, promiscuous (in relation to enzymes catalysing multiple substrates) and moonlighting (with two or more molecular functions), and difficult to be retrieved with a direct search in existing non-specific databases. The study of multifunctional proteins is an expanding research area aiming to elucidate the complexities of biological processes, particularly in humans, where multifunctional proteins play roles in various processes, including signal transduction, metabolism, gene regulation and cellular communication, and are often involved in disease insurgence and progression. The webserver allows searching by gene, protein and any associated structural and functional information, like available structures from PDB, structural models and interactors, using multiple filters. Protein entries are supplemented with comprehensive annotations including EC number, GO terms (biological pathways, molecular functions, and cellular components), pathways from Reactome, subcellular localization from UniProt, tissue and cell type expression from HPA, and associated diseases following MONDO, Orphanet and OMIM classification. MultiFacetedProtDB is freely available as a web server at: https://multifacetedprotdb.biocomp.unibo.it/.
Compartmentalization of androgen receptors at endogenous genes in living cells
Authors: Yavuz Selçuk , Kabbech Hélène , van Staalduinen Jente , Linder Simon , van Cappellen Wiggert A , Nigg Alex L , Abraham Tsion E , Slotman Johan A , Quevedo Marti , Poot Raymond A , Zwart Wilbert , van Royen Martin E , Grosveld Frank G , Smal Ihor , Houtsmuller Adriaan B
Published: October 2023

A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes—PTPRN2 or BANP—simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid–liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci.
Oral Nicotine Gum Discussions on Twitter: Content Analysis
Authors: Galimov Artur , Kirkpatrick Matthew G , Vassey Julia , Galstyan Ellen , Smith Ashley , Allem Jon-Patrick , Unger Jennifer B
Published: October 2023

Background

Oral nicotine gum such as LUCY, which comes in colorful packaging, mimicking traditional chewing gum, is becoming popular. Many brands of gum have not been approved by the FDA for smoking cessation. This study examined public discourse about, including sentiment toward, oral nicotine gum on Twitter.

Methods

We used Twitter’s Streaming Application Programming Interface to collect data from January 1, 2021, to December 21, 2021, using “nicotine gum” and/or “#nicotinegum” search terms (N = 19 171 unique tweets were collected). We used an inductive approach to become familiar with the data, generated a codebook, and conducted a content analysis on (n = 2152) tweets.

Results

Cessation (n = 716, 33.3%), personal experience (n = 370, 17.2%), and addiction to gum (n = 135, 6.3%) were the most prevalent themes. Cessation tweets primarily discussed cigarette smoking cessation (n = 418, 58.4% of cessation tweets) and successful cessation experiences (n = 155, 21.6%). Other identified themes pertained to using nicotine gum for cognitive enhancement or catching a “buzz” (n = 102, 4.7%), marketing (n = 98, 4.6%), using nicotine gum with other substances (n = 90, 4.2%), and adverse effects (n = 63, 2.9%). Sentiment analysis results revealed that 675 (44.2%) tweets were categorized as neutral, 605 (39.6%) tweets were classified as positive, and 248 tweets (16.2%) were negative.

Conclusions

About one-third of tweets in our corpus mentioned nicotine gum in the context of smoking cessation. Most nicotine gum-related posts conveyed positive and neutral sentiments. Future studies should consider adding novel nicotine gum-specific search terms as well as exploring other social media platforms to gain more insights about these products.

Implications

Our findings suggest that Twitter has the potential to track and facilitate conversations between those seeking cigarette cessation advice and those who have successfully quit tobacco by using nicotine gum. Monitoring of promotional content from nicotine gum companies is needed to ensure these products are not appealing to youth and nonusers of tobacco.
Systematic review: exploring outcomes of commercial and homemade blenderized tube-feeding regimens on feeding tolerance in pediatric patients
Authors: Velly Miguel Mariana , Haubrick Kevin
Published: October 2023

Context

Increasing numbers of patients and caregivers are requesting transition to blenderized tube feeding. There is a lack of systematic reviews addressing the outcomes of blenderized tube feeding.

Objective

The aim was to evaluate the association of blenderized tube feeding on feeding tolerance in enterally fed pediatric patients.

Data Sources

A literature search for articles from 2012–2022 using PubMed, Medline, Embase, and CINAHL yielded 78 articles.

Data Extraction

A description and evaluation of the study’s sample, purpose, and results were summarized for 9 studies using the Academy of Nutrition and Dietetics Evidence Analysis Library Worksheet.

Data Analysis

Nine studies were evaluated using the Evidence Analysis Library Quality Criteria checklist.

Conclusions

Studies demonstrated an improvement in vomiting (n = 7), gagging/retching and heartburn (n = 6), abdominal pain/upset and distension (n = 3), and diarrhea (n = 6) with blenderized tube feeding. The outcomes of blenderized tube feeding on gas (n = 5) and constipation (n = 9) are variable and remain unclear.

Systematic Review Registration

PROSPERO registration no. CRD42022369247.
The Benefit of Exercise in Patients With Cancer Who Are Receiving Chemotherapy: A Systematic Review and Network Meta-Analysis
Authors: Herranz-Gómez Aida , Suso-Martí Luis , Varangot-Reille Clovis , Barrachina-Gauchia Laia , Casaña José , López-Bueno Laura , Calatayud Joaquín , Cuenca-Martínez Ferran
Published: October 2023

Objective

This study aimed to determine which therapeutic exercise-based intervention is most effective in improving cardiorespiratory fitness (CRF) in patients with cancer receiving chemotherapy.

Methods

The authors conducted a systematic review with network meta-analysis in MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, SPORTDiscus, and Web of Science. The authors employed the Physiotherapy Evidence Database and the Revised Cochrane Risk of Bias Tool for Randomized Trials to assess the methodological quality and risk of bias, respectively.

Results

A total of 27 studies were included. Data were pooled using a random-effects model. Adding aerobic training (moderate to high intensity), with or without resistance training, to usual care versus usual care was statistically significant, with a small beneficial effect (aerobic training: standardized mean difference = 0.46; 95% CI= 0.17 to 0.75; aerobic and resistance training: standardized mean difference = 0.26; 95% CI = 0.00 to 0.52) for peak oxygen consumption at the postintervention assessment.

Conclusion

Therapeutic exercise-based interventions to improve short-term CRF in patients with cancer receiving chemotherapy should include moderate- to high-intensity aerobic exercise, with or without resistance training.

Impact

It is important to improve CRF in the oncological population due to its relationship with mortality. The results showed the benefit of exercise to improve cardiorespiratory fitness in the oncology population receiving chemotherapy treatment.
A Retrieved-Context Theory of Financial Decisions
Authors: Wachter Jessica A , Kahana Michael Jacob
Published: October 2023

Studies of human memory indicate that features of an event evoke memories of prior associated contextual states, which in turn become associated with the current event’s features. This retrieved-context mechanism allows the remote past to influence the present, even as agents gradually update their beliefs about their environment. We apply a version of retrieved-context theory, drawn from the literature on human memory, to explain three types of evidence in the financial economics literature: the role of early life experience in shaping investment choices, occurrence of financial crises, and the effect of fear on asset allocation. These applications suggest a recasting of neoclassical rational expectations in terms of beliefs as governed by principles of human memory.
Incidence and predictors of demyelinating disease in spondyloarthritis: data from a longitudinal cohort study
Authors: Remalante-Rayco Patricia , Espiritu Adrian I , Daghistani Yassir , Chim Tina , Atenafu Eshetu , Keshavarzi Sareh , Jha Mayank , Gladman Dafna D , Oh Jiwon , Haroon Nigil , Inman Robert D
Published: October 2023

Objectives

The objectives of this study were to investigate the incidence of demyelinating disease (DD) among SpA patients and to identify risk factors that predict DD in this patient population.

Methods

Axial SpA (axSpA) and PsA patients were identified from a longitudinal cohort database. Each group was analysed according to the presence or absence of DD. Incidence rates (IRs) of DD were obtained, with competing risk analysis. Cox regression analysis (with Fine and Gray’s method) was used to evaluate predictors of DD development.

Results

Among 2260 patients with follow-up data, we identified 18 DD events, corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, P = 0.01). The risk factors retained in the best predictive model for DD development included ever- (vs never-) smoking [hazard ratio (HR) 2.918, 95% CI 1.037–8.214, P = 0.0426], axSpA (vs PsA) (HR 8.790, 95% CI 1.242–62.182, P = 0.0294) and presence (vs absence) of IBD (HR 5.698, 95% CI 2.083–15.589, P = 0.0007). History of TNF-α inhibitor therapy was not a predictor of DD.

Conclusion

The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNF-α inhibitor use was not found to be a predictor of DD in this cohort.
Hepatocyte-specific deletion of small heterodimer partner protects mice against acetaminophen-induced hepatotoxicity via activation of Nrf2
Authors: Ghosh Priyanka , Magee Nancy , Akakpo Jephte Y , Ahamed Forkan , Eppler Natalie , Jones Elizabeth , Yu Yifan , He Lily , Lebofsky Margitta , Dai Hongyan , Jaeschke Hartmut , Ding Wen-Xing , Zhang Yuxia
Published: October 2023

Acetaminophen (APAP) overdose stands as the primary cause of acute liver failure in the United States. APAP hepatotoxicity involves hepatic glutathione (GSH) depletion and mitochondrial damage. To counteract the toxicity of APAP, the nuclear factor erythroid 2 like 2 (Nrf2) activates the expression of genes responsible for drug detoxification and GSH synthesis. In this study, we present evidence that the elimination of hepatocyte small heterodimer partner, a critical transcriptional repressor for liver metabolism, results in Nrf2 activation and protects mice from APAP-induced acute liver injury. Initial investigations conducted on wildtype (WT) mice revealed a swift downregulation of Shp mRNA within the first 24 h after APAP administration. Subsequent treatment of hepatocyte-specific Shp knockout (ShpHep−/−) mice with 300 mg/kg APAP for 2 h exhibited comparable bioactivation of APAP with that observed in the WT controls. However, a significant reduction in liver injury was observed in ShpHep−/− after APAP treatment for 6 and 24 h. The decreased liver injury correlated with a faster recovery of GSH, attributable to heightened expression of Nrf2 target genes involved in APAP detoxification and GSH synthesis. Moreover, in vitro studies revealed that SHP protein interacted with NRF2 protein, inhibiting the transcription of Nrf2 target genes. These findings hold relevance for humans, as overexpression of SHP hindered APAP-induced NRF2 activation in primary human hepatocytes. In conclusion, our studies have unveiled a novel regulatory axis involving SHP and NRF2 in APAP-induced acute liver injury, emphasizing SHP as a promising therapeutic target in APAP overdose-induced hepatotoxicity.
Indocyanine Green Lymphography in Conservative Lymphedema Therapy: A Scoping Review
Authors: Trevethan Megan , Patterson Freyr , Doig Emmah , Pigott Amanda
Published: October 2023

Background:

There is great potential but seemingly limited use of indocyanine green (ICG) lymphography to influence conservative lymphedema therapy clinical practice. This scoping review aimed to map existing evidence for ICG lymphography relating to conservative lymphedema therapy.

Methods:

A 6-staged scoping review framework of Arksey and O'Malley was used to guide the study. Protocol development included key stakeholder consultation. Searches were conducted in 5 databases with specialist librarian support. A 2-phase selection process undertaken by 2 researchers identified studies for inclusion. Conflicts were resolved by consensus. A subsequent 3-phase data extraction and quality appraisal process occurred. Key findings were presented in a descriptive numerical summary.

Results:

A total of 6316 records were identified, yielding 162 articles for inclusion. Categorization was made according to article type and purpose of ICG lymphography including lymphedema assessment (diagnosis and staging) and/or conservative therapy. Seventy-six empirical research articles with detailed reference to ICG lymphography were explored further.

Conclusion:

Current published research about ICG lymphography in conservative lymphedema therapy describes support for its use in lymphedema diagnosis, and proposes staging systems for lymphedema severity. Despite existing work, further exploration of effect on conservative therapy planning, clinical, and patient outcomes is necessary to consider future translation to clinical practice.
Risk Factors of Postoperative Coronal Balance Transition in Degenerative Lumbar Scoliosis
Authors: Ding Linyao , Sun Zhuoran , Li Weishi , Zeng Yan , Chen Ze , Qiu Weipeng , Hou Xiangyu , Yuan Lei
Published: October 2023

Study Design.

Retrospective radiographic study.

Objective.

To determine the potential risk factors influencing the transition of postoperative coronal balance in degenerative lumbar scoliosis (DLS) patients.

Summary of Background Data.

As time passes after surgery, the spinal sequence of DLS patients may dynamically shift from coronal balance to imbalance, causing clinical symptoms. However, the transition of postoperative coronal balance and its risk factors have not been effectively investigated.

Materials and Methods.

We included 156 DLS patients. The cohort was divided into immediate postoperative coronal balance with follow-up balance (N=73) and follow-up imbalance (N=21), immediate postoperative coronal imbalance (CIB) with follow-up balance (N=23), and follow-up imbalance (N=39). Parameters included age, sex, classification of coronal balance, coronal balance distance, fusion of L5 or S1, location of apical vertebra, apical vertebral translation (AVT), Cobb angle of the main curve and lumbar-sacral curve, tilt and direction of L4/5, tilt and direction of upper instrumented vertebra (UIV), and Cobb angle of T1-UIV. Statistical testing was performed using chi-square/Fisher exact test, t tests or nonparametric tests, correlation testing, and stepwise logistic regression.

Results.

We identified a significant difference in preoperative AVT, preoperative Cobb angle, and immediate postoperative UIV tilt between patients with and without follow-up balance. Logistic regression analysis demonstrated factors associated with follow-up CIB included preoperative AVT (P=0.015), preoperative Cobb angle (P=0.002), and tilt of immediate postoperative UIV (P=0.018). Factors associated with immediate postoperative CIB in patients with follow-up coronal balance were sex, correction ratio of the main curve, and direction of L4. Logistic regression analysis further identified a correction ratio of main curve ≤0.7 (P=0.009) as an important predictive factor.

Conclusion.

Patients with immediate postoperative coronal balance and higher preoperative AVT, preoperative Cobb angle, and tilt of immediate postoperative UIV were more likely to experience follow-up CIB. A correction ratio of the main curve ≤0.7 was an independent predictor of follow-up CIB.

Level of Evidence.

3.
Contrast-enhanced Magnetic Resonance Imaging in Patients With Dropped Head Syndrome
Authors: Endo Kenji , Nishimura Hirosuke , Sawaji Yasunobu , Aihara Takato , Suzuki Hidekazu , Konishi Takamitsu , Nagayama Kyohei , Yamamoto Kengo
Published: October 2023

Study Design.

This is a retrospective study of a consecutive case series of dropped head syndrome (DHS).

Objective.

To identify the characteristic features of contrast-enhanced magnetic resonance imaging (MRI) in DHS patients.

Summary of Background Data.

Isolated neck extensor myopathy DHS is thought to be caused by severe cervical extensor muscle weakness from age-related loss of elasticity. However, the MRI findings of the cervical extensor muscles in DHS patients have not yet been characterized.

Materials and Methods.

The subjects were 34 patients with isolated neck extensor myopathy DHS who underwent contrast-enhanced MRI within seven months after onset and 32 patients with age-matched cervical spondylosis or cervical soft-tissue tumor as controls. The presence of enhanced findings in the cervical extensor muscles, the involved cervical levels, and the characteristically enhanced shape of those muscles were evaluated using contrast-enhanced MRI.

Results.

In the DHS group, the contrast-enhanced MRI showed pronounced enhancement at splenius capitis in 34 cases, rhomboid in 23 cases, semispinalis cervicis in seven cases, and levator scapulae in three cases. In the non-DHS group, none of those extensor muscles were enhanced. The enhanced pattern was butterfly shaped in 29 cases (85.3%) and linear in five cases (14.7%). All were located at the spinous process attachment at C6 or C7 in the DHS group. In the non-DHS group, seven cases presented an enhanced image of the spinous process, with C5-6 in one case, C6 in five cases, and C7 in one case.

Conclusions.

In DHS, contrast-enhanced MRI showed intramuscular enhancement of the cervical extensor muscles, which was not present in non-DHS cases. The enhanced muscles included the splenius capitis muscle in all cases. These findings may be useful for developing a strategy for DHS treatment.
Decomposing the Black–White Racial Disparity in Severe Maternal Morbidity Risk: The Role of Hypertensive Disorders of Pregnancy
Authors: Labgold Katie , Howards Penelope P. , Drews-Botsch Carolyn , Dunlop Anne L. , Bryan J. Michael , Ruddock Tonia , Johnston Sabrina , Kramer Michael R.
Published: October 2023

Background:

To our knowledge, no studies have explicitly studied the role of hypertensive disorders of pregnancy (HDP) in racial disparities in severe maternal morbidity (SMM).

Methods:

Using causal mediation models, we estimated the proportion of the non-Hispanic (NH) Black–White racial disparity in risk of SMM that is explained through the pathway of HDP. We linked 2006–2019 Georgia hospital discharge records with vital statistics birth and fetal death records for NH Black and NH White birthing persons. We used G-estimation of a structural nested mean model to decompose the absolute racial disparity in the incidence of SMM into pathways operating through HDP.

Results:

NH Black birthing people experienced an excess 56 SMM events (95% confidence interval [CI] = 52, 59) per 10,000 delivery hospitalizations compared with NH White birthing people. If counterfactual disparity measure estimation assumptions hold, the estimated absolute disparity remaining after blocking the causal pathways through HDP was 41 SMM events per 10,000 deliveries (95% CI = 38, 44), suggesting that 26% (95% CI = 12, 40) of the absolute racial disparity would be eliminated if there was no contribution of HDP to SMM risk.

Conclusion:

Our results are consistent with the hypothesis that intervening to prevent HDP is an important (yet incomplete) pathway for reducing the excess risk among NH Black pregnancies compared with NH White pregnancies.
Latest advances in immuno-oncology for endometrial cancer: single-agent and combination regimens
Authors: Richardson Michael , Chase Dana M.
Published: October 2023

Purpose of review

The scope of immuno-oncology in endometrial cancer has changed rapidly in the last several years, requiring up-to-date knowledge for those who treat these patients.

Recent findings

This article will focus on molecular profiling, recent trials, and FDA approvals of targeted immuno-oncology medications in endometrial cancer. These include immune checkpoint inhibitors alone or with combination treatment.

The publication of the TCGA has led to significant focus on molecular subgroupings into POLEm, MMRd, NSMP, and p53m groups. For those patients with MMRd vs. MMRp tumors, there are indications for single agent immune checkpoint inhibitors with dostarlimab or pembrolizumab. For those with MMRp tumors, the addition of lenvatinib to pembrolizumab has proven clinical benefit. The recent publication of the RUBY and NRG-GY018 trials have shown clinical benefit in both subgroups with addition of immune checkpoint inhibitor to platinum-based chemotherapy. Now there is approval for use of dostarlimab in frontline chemotherapy and maintenance for advanced stage or recurrent endometrial cancer. Several upcoming trials investigating molecular subgroups from the TCGA are eagerly anticipated.
Modified Preparatory Intravascular Stenting Technique in Super-microsurgical Lymphaticovenular Anastomosis for the Treatment of Lymphedema
Authors: Nuri Takashi , Asaka Akinori , Otsuki Yuki , Ueda Koichi
Published: October 2023

Clinical studies have reported that lymphaticovenular anastomosis (LVA) is more effective for early-stage lymphedema. However, the diameter of lymphatic vessels in early-stage lymphedema is thin (only about 0.3 mm). In this article, we report a modified preparatory intravascular stenting technique (PIST) for LVA with smaller lymphatic vessels and present the results of its application for the treatment of secondary lymphedema. In this technique, a 9-0 nylon thread is inserted into the target lymphatic vessel. Then, the thread is pulled until its tip has entered the lymphatic vessel. After that, the thread is allowed to proceed into the lumen by pushing it. Finally, with the nylon in place, the lymphatic vessel is transected and the lumen is secured. In this report, we investigated the surgical time for LVA between 10 patients who underwent LVA with modified PIST (group A) and another group of 10 patients who underwent LVA without the technique (group B). Lymphatic lumen was secured at all sites where indocyanine green lymphangiography confirmed lymphatic flow. The average outer diameter of lymphatic vessels in group A and B were 0.36 mm and 0.53 mm, respectively. The average surgical time for LVA in group A was 136 minutes, which was significantly shorter than the 187 minutes in group B. Our results indicated that modified PIST can help secure the lymphatic lumen even when the lymphatic vessels are thin. As a result, this technique can significantly reduce the surgical time for this procedure.
Prospective Clinical Trial Evaluating the Outcomes Associated with the Use of Fresh Frozen Allograft Cartilage in Rhinoplasty
Authors: Wan Rou , Weissman Joshua P. , Williams Tokoya , Ullrich Peter J. , Joshi Chitang , Huffman Kristin , Galiano Robert D.
Published: October 2023

Background:

There are different types of grafts for rhinoplasty, each with certain advantages and disadvantages. Fresh frozen cadaveric costal allograft (CCA) provides an alternative to rhinoplasties. The aim of this study was to compare the outcomes of fresh frozen CCA and traditional autologous costal cartilage in cosmetic and reconstructive rhinoplasty procedures.

Methods:

This is a prospective, single-center, nonrandomized, open-label clinical trial. Objective assessment to evaluate warping, resorption, and displacement of the cartilage was achieved by measuring the differences of standardized values (deviation angle, nasofrontal angle, total facial convexity, nasofacial angle, and nasolabial angle) obtained at 6-months and 12-months postoperative follow-up on standard two-dimensional photographs (Δ = ∣measurement6 − measurement12∣). Subjective assessment was measured by the FACE-Q assessment.

Results:

Fifty eligible patients between March 2017 and October 2020 were included. The average age was 43.9 ± 16.6 years and the mean follow-up period was 14.8 months. In the control group, the changes (Δ) in the deviation angle and nasolabial angle were greater than in the CCA group (P < 0.05). In the CCA group, the mean score of satisfaction with nose improved at 6 months and 1 year postoperatively (P < 0.05). The mean score of satisfaction with nostrils and overall facial appearance also increased in the CCA group at 6 months postoperatively (P < 0.05). Six patients from the CCA group and 10 patients from the control group experienced postoperative complications.

Conclusions:

Fresh frozen CCA is a safe and reliable source of rhinoplasty grafts. It is aseptic, readily available, and free of donor site complications.
Sleep Quality in Patients With Ocular Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Liao Yinglin , Li Jing , Yang Jing , Zhao Wenxin , Chen Ziyan , Wu Shaowen , Jin Ling , Huang Fen , Liang Lingyi
Published: October 2023

Objectives:

To investigate the sleep quality in patients with ocular graft-versus-host disease (oGVHD) compared with patients without oGVHD after allogeneic hematopoietic stem cell transplantation (alloHCT) and healthy controls.

Methods:

This cross-sectional study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. Fifty healthy controls were also enrolled. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleep quality was defined as CPQSI score greater than 6.

Results:

Patients after alloHCT demonstrated a significantly higher CPQSI score than those of controls {7.0 [interquartile range (IQR) 5.0-10.0] vs. 5.5 [IQR 4.8–7.0], P=0.002}, especially in the oGVHD subgroup (7.5 [IQR 5.0–11.0] vs. 6.0 [IQR 5.0–8.0], P=0.04) with nearly double prevalence of poor sleep quality (58 [62%] vs. 18 [37%], P=0.006). Poor sleep quality was strikingly correlated with oGVHD diagnosis (adjusted odds ratio [OR]=2.55, 95% confidence interval [CI]: 1.02–6.34, P=0.04) and systemic immunosuppressants (adjusted OR=2.61, 95% CI: 1.32–5.71, P=0.02). Among the ocular parameters, poor sleep quality was significantly associated with higher ICOGCG score (adjusted OR=1.20, 95% CI: 1.03–1.39, P=0.02) and lower tear film break-up time (adjusted OR=0.85, 95% CI: 0.74–0.99, P=0.05).

Conclusions:

Poor sleep quality was associated with an increased severity of oGVHD and tear film instability in the long-term alloHCT survivorship.
New-onset chronic inflammatory demyelinating polyradiculoneuropathy after COVID-19 infection: a case report
Authors: Abedi Samakoush Mohammad , Davoodi Lotfollah , Khademian Mojtaba , Kargar-soleimanabad Saeed , Abedini Mohammad-Ali
Published: October 2023

Introduction and importance:

SARS-CoV-2 infection, besides respiratory symptoms, as cardinal manifestation, may present with neurological involvement. Immune-mediated polyradiculoneuropathy is one of the important neurological complications manifested by COVID-19 mainly includes Guillain–Barré syndrome (GBS), treatment-related fluctuation of GBS, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Also, there are several reports of COVID-19 vaccine-related GBS and CIDP. According to possible severe manifestations of neuropathies like respiratory failure, considering these complications for early diagnosis and treatment is very important.

Case presentation:

The authors presented a 67-year-old woman with severe weakness in upper and lower extremities, the patient was diagnosed as case with CIDP initiated after COVID-19 virus infection and/or vaccination that experienced one relapse in 11 months. In both episodes, treatment with intravenous immunoglobulin started and the patient respond.

Clinical discussion:

To the best of our knowledge, this is one of the first reported cases with a typical chronic course of CIDP associated with COVID-19 virus infection and/or vaccination.

Conclusion:

Considering this complication and differentiation between GBS and CIDP, and then initiating maintenance therapy can prevent long-term disability.
Long-term patency of bypass to the right atrium as a last resort in two hemodialysis patients: case report
Authors: Banana Youssef , Boukabous Sara , El malki Hicham , Rezziki Abdellah , Belarbi Adam , Haddiya Intissar , Bentata Yassamine , Moutaouekkil El Mehdi , Benzirar Adnane , El Mahi Omar
Published: October 2023

Introduction:

Central venous occlusion (CVO), which is caused by central venous catheters in haemodialysis patients , remains a challenge in vascular surgery.

Case presentation:

The authors report data evaluating bypass graft patency and complications of two patients with CVO who have benefited from a subclavian artery to right atrium bypass using polytetrafuloroetylene. The first patient , underwent three times an angioplasty of the atrio prothetic anastomosis , finally the graft failed at 12 month. The second one, presented a steal syndrome with ischaemia of the right upper limb immediately postoperatively. Three months after the procedure , she underwent an angiographic control that showed a stenosis of the protheto atrial junction.

Clinical discussion:

Central venous occlusion in patients with end-stage kidney disease is most often due to central venous catheters. Although the endovascular therapy is the first-line approach to the treatment of CVO, the surgical bypass to the right atrium is often the last resort to preserve adequate vascular access in haemodialysis patients, with CVO. The autologous vein and bovine arterial bypass remains better than polytetrafuloroetylene grafts in terms of long-term patency. Only few cases have been reported un the literature , besides no long-term outcome data has been previously reported.

Conclusion:

Long-term secondary patency of bypass to the right atrium can be achieved, but requires strict follow-up, and multiple endovascular procedures to maintain the bypass access.
Aneurysmal bone cyst of the mandible: a rare case report and literature review
Authors: Yahaya James J. , Morgan Emmanuel D. , Abraham Zephania S. , Othieno Emmanuel
Published: October 2023

Introduction and importance:

Aneurysmal bone cysts (ABCs) are benign, non-neoplastic cystic lesions composed of multiple blood-filled cavities, which are separated by connective tissue septa and they constitute ~6 and 1.5% of all cases of the skull and jaws lesions, respectively.

Case presentation:

Herein, the case of an 80-year-old male with a histologically confirmed diagnosis of ABC involving the body of the left mandible was presented. The patient underwent partial mandiblectomy after confirmation of the diagnosis using orthopantomography, a computed tomography scan, and a tissue biopsy. The patient was free from pain after 1-year of follow-up, and the control orthopantomography showed no evidence of recurrence. This was followed by reconstruction of the healed part of the bone with titanium plates and a piece of bone from the lateral two-thirds of the left femur and thereafter he was cosmetically well.

Clinical discussion:

Patients with ABCs present with expansile and radiolucent bone lesions, which may be associated with displacement and loss of teeth due to alveolar bone erosion. Complete excision of the lesions is mandatory for the prevention of recurrence and increased morbidity.

Conclusion:

ABCs that involve the jaws are extremely rare and are more likely to pose a diagnostic challenge as they are more likely to be confused clinically with other expansile radiolucent bone lesions such as ameloblastoma, osteoblastoma, and giant cell tumor among many others. Also, those with extensive bone matrix formation may sometimes be confused histologically with other bone forming tumors including osteosarcoma. Recurrence is common but it can be avoided or minimized by complete resection of the lesion.
Ultrasound-guided quadratus lumborum block: a powerful way for reducing postoperative pain
Authors: Long Xuechen , Yin Yibo , Guo Wenjun , Tang Ling
Published: October 2023

Ultrasound-guided quadratus lumborum block (QLB) has been gradually carried out in clinical practice. However, some clinical evidence is contradictory, and no studies have summarized and described these results. The authors reviewed the anatomical characteristics of QLB and summarized the advantages and disadvantages of four puncture methods, so as to facilitate the clinical application of QLB.
The landscape of neuroscience research in Africa: current state, progress, and challenges; a perspective
Authors: Aderinto Nicholas , Abdulbasit Muili , Olatunji Gbolahan , Edun Mariam
Published: October 2023

The field of neuroscience research in Africa has witnessed significant advancements in recent years, contributing to understanding the brain and neurological disorders. This paper provides an overview of the current state of neuroscience research in Africa, highlighting the progress made, ongoing efforts, and the challenges researchers face. Despite limited resources and funding constraints, African scientists have made remarkable strides in various areas of neuroscience. Collaborative networks and international partnerships have been crucial in advancing education, research infrastructure, and capacity building in the field. Institutions in countries such as Egypt, Ghana, South Africa, Nigeria, Tunisia, and Morocco have emerged as key hubs for neuroscience research, fostering a growing community of researchers dedicated to unravelling the complexities of the brain. Efforts in neuroscience research have encompassed diverse domains, including neurogenomics, neuroimaging, neurophysiology, neurorehabilitation, and neuroepidemiology. Studies have focused on investigating genetic factors underlying neurological conditions, exploring the neural mechanisms of cognition and behaviour, and developing innovative therapeutic approaches for neurological disorders. However, challenges persist in the African neuroscience research landscape. Limited funding remains a significant barrier, hindering the establishment of well-equipped laboratories, access to advanced technologies, and support for research projects. Addressing these concerns is crucial to ensure research outcomes’ integrity, validity, and relevance. Looking ahead, strategic interventions are required to address these challenges and further advance neuroscience research in Africa.
Clips closure versus endoloop ligation in laparoscopic appendectomy: a systematic review and meta-analysis of comparative studies
Authors: Poon Samuel Ho Ting , Law Sui Yuen , Lai Alex Ting Yeung
Published: October 2023

Introduction:

Appendiceal stump closure (ASC) is a key step in performing laparoscopic appendicectomy. Currently, there is no gold standard method to achieve this goal. The ideal method should be safe, easily available, and have a short learning curve. Out of all those appendiceal stump closure methods, the use of hem-o-Lok demonstrates its feasibility in replacing the traditionally used endoloop. In this systematic review and meta-analysis, the authors aim to review the currently available evidence addressing the topic of interest.

Method:

The PubMed and Embase databases were searched with the paired search terms appendicitis, clip, and endoloop by two authors separately. The quality of the randomized controlled trials was assessed with the Cochrane risk of bias tool, and the quality of the observational studies was assessed with the Newcastle-Ottawa scale. Meta-analysis was conducted with Cochrane Review Manager version 5.4.

Result:

Eighteen studies were included for quantitative analysis. The appendiceal stump closure time was shortened by 2 min 7 s using a hem-o-lok with 95% CI 1 min 48 s–2 min 26 s, p less than 0.00001. The pooled results of 6 randomized controlled trials demonstrated a statistically significant reduction in operative time of 5.15 min from adopting the hem-o-lok approach (p=0.001, 95% CI −2.05 to −8.24 min). Both endoloop and hem-o-lok demonstrated a comparable postoperative hospital stay and infective complication profile.

Conclusion:

The application of Hem-o-Lok demonstrates a comparable to endoloop ligation in terms of operative time and a potential benefit on the complication. When considering financial and technical aspects, it serves as an alternative to endoloop.
Potential application of anti-osteoporotic therapy to relieve sarcopenia in the elderly
Authors: Li YunGui , Li XiaoBing , Kong ZhaoRong , Yin BangFang , Lan ZongLin , Li HongJian
Published: October 2023

Sarcopenia is a progressive and systemic skeletal muscle disorder associated with aging that usually occurs with age in the elderly. Sarcopenia currently lacks effective pharmacological treatment modalities. Multiple pharmacological intervention modalities are available for osteoporosis, a comprehensive disease characterized by decreased systemic bone mass, degradation of bone microarchitecture, and increased bone fragility. Several recent studies have shown an extremely strong correlation between sarcopenia and osteoporosis, leading to the concept of “osteosarcopenia”. Therefore, it is possible to alleviate sarcopenia simultaneously by improving osteoporosis.
Reconstructive surgery and adjuvant radiotherapy for the multimodal approach in oral cancer: a single cancer centre experience
Authors: Bernaola-Paredes Wilber Edison , Rodrigues Monica Lucia , Carvalho Henrique Perez , dos Santos Bitencourt Fernando , Coutinho Marcelo Carvalho , D’Almeida Costa Felipe , Vallejo-Rosero Kleber Arturo , Marquez-Zambrano Jose Agustin , Pellizzon Antonio Cassio Assis
Published: October 2023

Introduction and importance:

Ablative surgery for oral cancer, irrespective of the histological subtype, causes large tissue defects, functional and aesthetic damage. Microsurgical free flaps have been widely used in reconstruction after resection, with satisfactory success rates in conjunction with adjuvant radiotherapy (RT). This study aims to describe our clinical institutional experience based on the multimodal treatment performed in four cases diagnosed with oral squamous cell carcinoma with the use of different microvascular free flaps and RT.

Case series presentation:

Four patients underwent reconstructive microsurgery after surgical resection of oral cancer, using three types of free flap: radial forearm fasciocutaneous, osteomyocutaneous fibular, and anterolateral thigh musculocutaneous flaps; RT was performed in Case 2 and Case 3. In the period of 3 years after microsurgical reconstruction and RT, flaps remain clinically stable without failure signs in full patients submitted to multimodal treatment.

Clinical discussion:

After resection of oral carcinomas, extensive tissue defects can be successfully treated with reconstructive microsurgery using different types of microvascular free flaps. RT for locoregional control is a feasible option and did not seem to interfere with the survival of flaps.

Conclusion:

An enhance long-term follow-up to assess overall and disease-free survival rates and quality of life must be carried out; however, cohort studies would be necessary for better understanding of the role of each treatment in the multimodal scheme.
Bone Echinococcosis Mimicking Malignancy on FDG PET
Authors: Takenaka Junki , Hirata Kenji , Watanabe Shiro , Takahata Masahiko , Kudo Kohsuke
Published: October 2023

MRI revealed a thoracic vertebrae lesion in a 40-year-old woman with back pain. She was referred to our institution; MRI demonstrated a mass from the second to the fifth thoracic vertebra and compression fractures. CT revealed a splenic mass, multiple pulmonary nodules, and low-density masses in the liver. 18F-FDG PET/CT showed increased uptake (SUVmax, 10.6) in the peripheral rim of the thoracic vertebra mass, with central parts showing lower uptake than the peripheral rim. The splenic mass exhibited increased accumulation (SUVmax, 4.8). The thoracic spine lesion was fixed; a biopsy was performed. Alveolar echinococcosis was confirmed immunologically. Alveolar echinococcosis can present with bone lesions. It must be differentiated from malignancy.
Whipple Disease Misdiagnosed as Lymphoma by 18F-FDG PET/CT: A Case Study
Authors: Cheng You , Lu Kai-yu , Shao Dan
Published: October 2023

Whipple disease is a rare disorder caused by infection with the gram-positive bacterium Tropheryma whipplei. It can invade various organs and systems of the whole body. This case report describes a patient with invasion of multiple lymph nodes throughout the body misdiagnosed as lymphoma by PET/CT.