bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of JAK inhibitors in paradoxical reaction through immune-related dermatoses
Authors: Zhang Yaxin , Jiang Guan
Published: February 2024

Biologics play a positive and effective role in the treatment of immune-related dermatoses. However, many other immune-related diseases have also manifested along with biologics treatment. Paradoxical reaction through immune-related dermatoses refer to the new onset or exacerbation of other immune-mediated dermatoses (mainly psoriasis and atopic dermatitis) after biologics treatment of inflammatory dermatoses (mainly psoriasis and atopic dermatitis), such as new atopic dermatitis (AD) in psoriasis (PsO) treatment and new PsO in AD treatment. A common genetic background and Inflammatory pathway are possible pathogenesis. Faced with paradoxical reactions, the choice of therapy needs to be directed toward therapies effective for both diseases, such as Janus kinase (JAK) inhibitors. The Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway plays an important role in the inflammatory pathway, and has been widely used in the treatment of AD and PsO in recent years. This article focuses on JAK inhibitors such as tofacitinib, baricitinib, ruxolitinib, Abrocitinib, upadacitinib, and deucravacitinib, to explore the possible application in treatment of paradoxical reactions. Common side effects, baseline risk factors and safety use of JAK inhibitors were discussed.
Proteomics analysis reveals differential acclimation of coastal and oceanic Synechococcus to climate warming and iron limitation
Authors: Schiksnis Cara , Xu Min , Saito Mak A. , McIlvin Matthew , Moran Dawn , Bian Xiaopeng , John Seth G. , Zheng Qiang , Yang Nina , Fu Feixue , Hutchins David A.
Published: February 2024

In many oceanic regions, anthropogenic warming will coincide with iron (Fe) limitation. Interactive effects between warming and Fe limitation on phytoplankton physiology and biochemical function are likely, as temperature and Fe availability affect many of the same essential cellular pathways. However, we lack a clear understanding of how globally significant phytoplankton such as the picocyanobacteria Synechococcus will respond to these co-occurring stressors, and what underlying molecular mechanisms will drive this response. Moreover, ecotype-specific adaptations can lead to nuanced differences in responses between strains. In this study, Synechococcus isolates YX04-1 (oceanic) and XM-24 (coastal) from the South China Sea were acclimated to Fe limitation at two temperatures, and their physiological and proteomic responses were compared. Both strains exhibited reduced growth due to warming and Fe limitation. However, coastal XM-24 maintained relatively higher growth rates in response to warming under replete Fe, while its growth was notably more compromised under Fe limitation at both temperatures compared with YX04-1. In response to concurrent heat and Fe stress, oceanic YX04-1 was better able to adjust its photosynthetic proteins and minimize the generation of reactive oxygen species while reducing proteome Fe demand. Its intricate proteomic response likely enabled oceanic YX04-1 to mitigate some of the negative impact of warming on its growth during Fe limitation. Our study highlights how ecologically-shaped adaptations in Synechococcus strains even from proximate oceanic regions can lead to differing physiological and proteomic responses to these climate stressors.
Response of serum biochemical profile, antioxidant enzymes, and gut microbiota to dietary Hong-bailanshen supplementation in horses
Authors: Ding Jinxue , Gu Bolin , Meng Jinwu , Hu Mengxin , Wang Wenjia , Liu Jiaguo
Published: February 2024

Background

Traditional Chinese medicine (TCM) is widely used in humans and animals, which is very important for health. TCM affects the body ‘s immunity and changes in intestinal flora. This study was conducted to investigate the effects of dietary Hong-bailanshen (HBLS) supplementation in horses on serum biochemical profile, antioxidant enzymes and gut microbiota.

Methods

In this study, five horses were selected. On day 0, 14, 28, blood samples and feces were collected on days 0, 14, and 28 to analyse gut microbiota, serum biochemical and redox indexes.

Results

The results showed that the addition of HBLS to horse diets significantly decreased the level of alanine aminotransferase, alkaline phosphatase, creatine kinase and malondialdehyde (p < 0.05, p < 0.01) and significantly increased the activity of total antioxidant capacity, superoxide dismutase and catalase (p  < 0.05, p  < 0.01). Compared with day 14, the levels of alanine aminotransferase, alkaline phosphatase and creatine kinase were significantly decreased; however, the level of catalase was significantly increased in the horses continuously fed with HBLS for 28 days (p  < 0.05, p < 0.01). Alpha diversity analysis was performed that chao1 (p  < 0.05), observed_specicies, faith’pd and goods_coverage upregulated in the horses fed HBLS. A total of 24 differential genera were detected adding HBLS to diet increased the abundance of Bacillus, Lactobacillaceae, Leuconostocaceae, Christensenellaceae, Peptostreptococcaceae, Faecalibacterium, Erysipelotrichaceae, Pyramidobacter, Sphaerochaeta, WCHB1-25, Bacteria, Oscillospira, and Acetobacteraceae, while reduced Aerococcus, EtOH8, Syntrophomonas, Caulobacter, Bradyrhizobiaceae, W22, Succinivibrionaceae, and Desulfovibrio (p < 0.05, p < 0.01).

Conclusion

Adding HBLS to the diet could be a potentially effective strategy to improve horses’ health.
Endophytic fungi in buckwheat seeds: exploring links with flavonoid accumulation
Authors: Zhong Lingyun , Niu Bei , Xiang Dabing , Wu Qi , Peng Lianxin , Zou Liang , Zhao Jianglin
Published: February 2024

Buckwheat is a famous edible and medicinal coarse cereal which contain abundant of bioactive flavonoids, such as rutin. In this study, the composition and diversity of endophytic fungi in eight different buckwheat seeds were analyzed by high-throughput sequencing of ITS rDNA. Results showed that, the fungal sequences reads were allocated to 272 OTUs, of them, 49 OTUs were shared in eight buckwheat seeds. These endophytic fungi could be classified into 6 phyla, 19 classes, 41 orders, 79 families, 119 genera, and 191 species. At genus level, Alternaria sp. was the domain fungal endophyte. Besides, fungal endophytes belonged to the genera of Epicocum, Cladosporium, Botrytis, Filbobasidium, Stemphylium, and Vishniacozyma were highly abundant in buckwheat seeds. The total flavonoids and rutin contents in tartary buckwheat cultivars (CQ, XQ, CH, K2) were much higher than those in common buckwheat cultivars (HT, T2, T4, T8). For tartary buckwheat cultivars, the total flavonoids and rutin contents were ranging from 2.6% to 3.3% and 0.9% to 1.3%, respectively. Accordingly, the tartary buckwheat samples displayed stronger antioxidant activity than the common buckwheat. Spearman correlation heat map analysis was successfully found that certain fungal species from the genera of Alternaria, Botryosphaeria, Colletorichum and Diymella exhibited significant positive correlation with flavonoids contents. Results of this study preliminary revealed the fungi-plant interaction relationship at secondary metabolite level, and could provide novel strategy for increasing the flavonoids accumulation of buckwheat seeds, as well as improving their quality.
Advancements in LAM-based diagnostic kit for tuberculosis detection: enhancing TB diagnosis in HIV-negative individuals
Authors: Gao Man , Wu Qianhong , Wang Xinhong , Sun Xiuli , Li Meng , Bai Guanghong
Published: February 2024

Objective

The purpose of this study was to investigate the diagnostic value of urine lipoarabinomannan (LAM) detection based on chemiluminescence assay for pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in HIV-negative individuals.

Methods

A total of 215 patients and 37 healthy individuals were included according to inclusion and exclusion criteria, including 173 cases of PTB and 42 cases of EPTB. Sputum smears, sputum culture, TB-RNA, GeneXpert, and urine LAM results were obtained from all patients before treatment. Using the composite reference standard as the reference, the diagnostic performance of these methods for PTB and EPTB was evaluated, and the diagnostic performance and cost-effectiveness of different combinations were analyzed.

Results

In PTB, LAM exhibited the highest sensitivity (55.49%), followed by GeneXpert (44.51%). In EPTB, LAM also had the highest sensitivity (40.48%), followed by GeneXpert (33.33%). When combined with one method, LAM combined with GeneXpert showed the highest sensitivity for both PTB (68.79%) and EPTB (61.9%). When combined with two methods, culture, GeneXpert, and LAM showed the highest sensitivity for both PTB (73.99%) and EPTB (69.05%). In terms of cost-effectiveness analysis, the price of LAM was significantly lower than that of GeneXpert ($129.82 vs. $275.79 in PTB and 275.79 vs. 502.33 in EPTB). Among all combinations, the combination of LAM and sputum smear had the lowest cost, with prices of $124.94 for PTB and $263.72 for EPTB.

Conclusion

Urine LAM detection based on chemiluminescence assay can be used as an adjunct diagnostic tool for PTB and EPTB in HIV-negative individuals. This facilitates expanding the current application of urine LAM from solely HIV-positive populations to the general population. LAM detection can overcome the limitations of obtaining clinical samples, and its ease of sample acquisition will be beneficial for its broader application in a larger scope. For economically better-off areas, we recommend using a combination of LAM + GeneXpert+culture for higher sensitivity; for economically disadvantaged areas, LAM + smear microscopy combination can provide a quick and accurate diagnosis of tuberculosis at a lower cost.
Sex-driven variability in TSPO-expressing microglia in MS patients and healthy individuals
Authors: Laaksonen Sini , Saraste Maija , Nylund Marjo , Hinz Rainer , Snellman Anniina , Rinne Juha , Matilainen Markus , Airas Laura
Published: February 2024

Background

Males with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear.

Objective

We hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression.

Methods

The study cohort consisted of 102 MS patients (mean (SD) age 45.3 (9.7) years, median (IQR) disease duration 12.1 (7.0–17.2) years, 72% females, 74% relapsing–remitting MS) and 76 age- and sex-matched healthy controls. TSPO-expressing microglia were measured using the TSPO-binding radioligand [11C](R)-PK11195 and brain positron emission tomography (PET). TSPO-binding was quantified as distribution volume ratio (DVR) in normal-appearing white matter (NAWM), thalamus, whole brain and cortical gray matter (cGM).

Results

Male MS patients had higher DVRs compared to female patients in the whole brain [1.22 (0.04) vs. 1.20 (0.02), p = 0.002], NAWM [1.24 (0.06) vs. 1.21 (0.05), p = 0.006], thalamus [1.37 (0.08) vs. 1.32 (0.02), p = 0.008] and cGM [1.25 (0.04) vs. 1.23 (0.04), p = 0.028]. Similarly, healthy men had higher DVRs compared to healthy women except for cGM. Of the studied subgroups, secondary progressive male MS patients had the highest DVRs in all regions, while female controls had the lowest DVRs.

Conclusion

We observed higher TSPO-binding in males compared to females among people with MS and in healthy individuals. This sex-driven inherent variability in TSPO-expressing microglia may predispose male MS patients to greater likelihood of disease progression.
Between neurons and networks: investigating mesoscale brain connectivity in neurological and psychiatric disorders
Authors: Caznok Silveira Ana Clara , Antunes Andre Saraiva Leão Marcelo , Athié Maria Carolina Pedro , da Silva Bárbara Filomena , Ribeiro dos Santos João Victor , Canateli Camila , Fontoura Marina Alves , Pinto Allan , Pimentel-Silva Luciana Ramalho , Avansini Simoni Helena , de Carvalho Murilo
Published: February 2024

The study of brain connectivity has been a cornerstone in understanding the complexities of neurological and psychiatric disorders. It has provided invaluable insights into the functional architecture of the brain and how it is perturbed in disorders. However, a persistent challenge has been achieving the proper spatial resolution, and developing computational algorithms to address biological questions at the multi-cellular level, a scale often referred to as the mesoscale. Historically, neuroimaging studies of brain connectivity have predominantly focused on the macroscale, providing insights into inter-regional brain connections but often falling short of resolving the intricacies of neural circuitry at the cellular or mesoscale level. This limitation has hindered our ability to fully comprehend the underlying mechanisms of neurological and psychiatric disorders and to develop targeted interventions. In light of this issue, our review manuscript seeks to bridge this critical gap by delving into the domain of mesoscale neuroimaging. We aim to provide a comprehensive overview of conditions affected by aberrant neural connections, image acquisition techniques, feature extraction, and data analysis methods that are specifically tailored to the mesoscale. We further delineate the potential of brain connectivity research to elucidate complex biological questions, with a particular focus on schizophrenia and epilepsy. This review encompasses topics such as dendritic spine quantification, single neuron morphology, and brain region connectivity. We aim to showcase the applicability and significance of mesoscale neuroimaging techniques in the field of neuroscience, highlighting their potential for gaining insights into the complexities of neurological and psychiatric disorders.
Carbohydrate mouth rinse failed to reduce central fatigue, lower perceived exertion, and improve performance during incremental exercise
Authors: Pires Flávio O. , Pinheiro Fabiano A. , Brietzke Cayque , Franco-Alvarenga Paulo Estevão , Veras Katherine , de Matos Eugênia C. T. , Rodacki André L. F. , Ugrinowitsch Carlos
Published: February 2024

We examined if carbohydrate (CHO) mouth rinse may reduce central fatigue and perceived exertion, thus improving maximal incremental test (MIT) performance. Nine recreational cyclists warmed up for 6 min before rinsing a carbohydrate (CHO) or placebo (PLA) solution in their mouth for 10 s in a double-blind, counterbalanced manner. Thereafter, they performed the MIT (25 W·min−1 increases until exhaustion) while cardiopulmonary and ratings of perceived exertion (RPE) responses were obtained. Pre- to post-MIT alterations in voluntary activation (VA) and peak twitch torque (Tw) were determined. Time-to-exhaustion (p = 0.24), peak power output (PPO; p = 0.45), and V̇O2MAX (p = 0.60) were comparable between conditions. Neither treatment main effect nor time–treatment interaction effect were observed in the first and second ventilatory threshold when expressed as absolute or relative V̇O2 (p = 0.78 and p = 0.96, respectively) and power output (p = 0.28 and p = 0.45, respectively) values, although with moderate-to-large effect sizes. RPE increased similarly throughout the tests and was comparable at the ventilatory thresholds (p = 0.56). Despite the time main effect revealing an MIT-induced central and peripheral fatigue as indicated by the reduced VA and Tw, CHO mouth rinse was ineffective in attenuating both fatigues. Hence, rinsing the mouth with CHO was ineffective in reducing central fatigue, lowering RPE, and improving MIT performance expressed as PPO and time-to-exhaustion. However, moderate-to-large effect sizes in power output values at VT1 and VT2 may suggest some beneficial CHO mouth rinse effects on these MIT outcomes.
Blood urea nitrogen to serum albumin ratio is associated with all-cause mortality in patients with AKI: a cohort study
Authors: Shi Yue , Duan Hangyu , Liu Jing , Shi Xiujie , Zhang Yifan , Zhang Qi , Zhao Mingming , Zhang Yu
Published: February 2024

Background

This study aims to investigate the relationship between blood urea nitrogen to serum albumin ratio (BAR) and all-cause mortality in patients with acute kidney injury (AKI) and evaluate the effect of BAR on the prognosis of AKI.

Methods

Adult patients with AKI admitted to the ICU in the Medical Information Mart for Intensive Care IV (MIMIC-IV) were selected in a retrospective cohort study. BAR (mg/g) was calculated using initial blood urea nitrogen (mg/dl)/serum albumin (g/dl). According to the BAR, these patients were divided into quartiles (Q1–Q4). Kaplan–Meier analysis was used to compare the mortality of the above four groups. Multivariate Cox regression analysis was used to evaluate the association between BAR and 28-day mortality and 365-day mortality. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated, and the subgroup analysis was finally stratified by relevant covariates.

Results

A total of 12,125 patients with AKI were included in this study. The 28-day and 365-day mortality rates were 23.89 and 39.07%, respectively. Kaplan–Meier analysis showed a significant increase in all-cause mortality in patients with high BAR (Log-rank p < 0.001). Multivariate Cox regression analysis showed that BAR was an independent risk factor for 28-day mortality (4.32 < BAR≤7.14: HR 1.12, 95% CI 0.97–1.30, p = 0.114; 7.14 < BAR≤13.03: HR 1.51, 95% CI 1.31–1.75, p < 0.001; BAR>13.03: HR 2.07, 95% CI 1.74–2.47, p < 0.001; Reference BAR≤4.32) and 365-day mortality (4.32 < BAR≤7.14: HR 1.22, 95% CI 1.09–1.36, p < 0.001; 7.14 < BAR≤13.03: HR 1.63, 95% CI 1.46–1.82, p < 0.001; BAR>13.03: HR 2.22, 95% CI 1.93–2.54, p < 0.001; Reference BAR ≤ 4.32) in patients with AKI. The AUC of BAR for predicting 28-day mortality and 365-day mortality was 0.649 and 0.662, respectively, which is better than that of blood urea nitrogen and sequential organ failure assessment. In addition, subgroup analysis showed a stable relationship between BAR and adverse outcomes in patients with AKI.

Conclusion

BAR is significantly associated with increased all-cause mortality in patients with AKI. This finding suggests that BAR may help identify people with AKI at high risk of mortality.
Immunomodulation of nutritional formula containing epigallocatechin-3-gallate, ginseng extract, and polydextrose on inflammation and macrophage polarization
Authors: Wang Yi , Hu Yaozhong , Niu Zhenhua , Zhang Xuejiao , Fan Dancai , Ji Xuemeng , Lv Huan , Wang Shuo , Zhao Yanrong
Published: February 2024

Single nutrient likes polyphenol or dietary fiber have been exhaustively investigated to validate their positive intervention in health or disease. Meanwhile, the common interaction of inner systems with the nutrient complex has not been well elucidated, which raises the scientific issue of the modulatory effect of the nutrient complex on immunity. The representative prebiotics of epigallocatechin-3-gallate (EGCG), ginseng extract, and polydextrose (PDX) were selected on behalf of the classification of polyphenol, flavone or polysaccharides, and dietary fiber to generally cover the daily food intake in this study to explore their intervention in inflammation and macrophage polarization. The intervention of selected nutrients on inflammation and macrophage polarization has been evaluated against macrophages to unveil their comprehensive effects. The synergistic effect of selected nutrients was demonstrated by inhibiting M1 macrophage polarization and the promotion of M2 macrophage polarization. Then, the nutrient formula was set up to verify the intervention effect, and the results revealed the significant inhibition of cell inflammation and the effect on cell proliferation through promoting the cell cycle in the G2 phase. The nutrient complex could inhibit M1 macrophage polarization to inhibit M1-mediated inflammation and promote M2 macrophages for anti-inflammatory effect and enhance cell phagocytosis. Moreover, the varied intervention effects of the nutrient complex with different formulas could be summarized. In general, the formula containing EGCG, ginseng extract, and PDX was demonstrated to possess an enhanced immunomodulatory effect on cell inflammation and macrophage polarization, which could potentially inspire the investigation of complex nutrients in health and diseases.
Geographical and temporal differences in gastric and oesophageal cancer registration by subsite and morphology in Europe
Authors: Giusti Francesco , Martos Carmen , Bettio Manola , Negrão Carvalho Raquel , Zorzi Manuel , Guzzinati Stefano , Rugge Massimo
Published: February 2024

Background

Gastric and oesophageal cancers pose a serious public health concern. In 2020 a total of 189,031 incident cases (136,038 stomach, 52,993 oesophagus) and 142,508 deaths (96,997 stomach, 45,511 oesophagus) were estimated in Europe. Oesophago-gastric cancers are a heterogeneous disease, with different aetiology and epidemiology for the various topographic subsites and main histopathological types. Topography subsite and morphology is key information to allow differentiating oesophago-gastric cancers. Correct registration and coding of such variables are fundamental in allowing proper description of the epidemiology of different subsites and histopathological types of oesophago-gastric cancers. The aim of this article is to highlight geographical and temporal variability in topography and morphology of oesophago-gastric cancers observed in Europe in the considered period.

Methods

Data collected in the framework of the ENCR-JRC (European Commission’s Joint Research Centre) data call and feeding the European Cancer Information System (ECIS) were used to assess the variability of topography and morphology registration of gastric and oesophageal cancer in Europe in the period 1995-2014. Malignant cancers of the stomach and the oesophagus were selected following, respectively, topography codes C16 and C15 of the International Classification of Diseases for Oncology, third edition (ICD-O-3). Analyses were performed by subsite, morphology group, year, sex, and European region.

Results

A total of 840,464 incident cases occurring in the period 1995-2014 – 579,264 gastric (67.2%) and 276,260 (32.8%) oesophageal carcinomas – was selected for the analysis. Data was recorded by 53 PBCRs (9 based in Northern Europe, 14 in Western Europe, 3 in Eastern Europe and 27 in Southern Europe) from 19 countries.

Conclusion

A wide variability in oesophago-gastric cancers topographic subsites and histopathological types patterns was observed, with a corresponding improvement in accuracy of registration in the analysis period. PBCRs are ideally placed to guide the epidemiological evaluations of such a complex group of diseases, in collaboration with clinicians, patients and other public health stakeholders.
Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer
Authors: Yang Kyungmi , Noh Jae Myoung , Park Hye Yun , Yoo Hongseok , Shin Sun Hye , Pyo Hongryull
Published: February 2024

Purpose

To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection.

Methods

Data from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity.

Results

The median follow-up was 28.9 months (range, 1.1–62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months’ post-PBT (p=0.047) and was maintained until 13 months (p=0.028).

Conclusion

Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.
Retrospective cohort study investigating association between precancerous gastric lesions and colorectal neoplasm risk
Authors: Pan Hui , Zhang Yu-Long , Fang Chao-Ying , Chen Yu-Dai , He Li-Ping , Zheng Xiao-Ling , Li Xiaowen
Published: February 2024

Background

Colorectal cancer (CRC) is considered the most prevalent synchronous malignancy in patients with gastric cancer. This large retrospective study aims to clarify correlations between gastric histopathology stages and risks of specific colorectal neoplasms, to optimize screening and reduce preventable CRC.

Methods

Clinical data of 36,708 patients undergoing gastroscopy and colonoscopy from 2005-2022 were retrospectively analyzed. Correlations between gastric and colorectal histopathology were assessed by multivariate analysis. Outcomes of interest included non-adenomatous polyps (NAP), conventional adenomas (CAs), serrated polyps (SPs), and CRC. Statistical analysis used R version 4.0.4.

Results

Older age (≥50 years) and Helicobacter pylori infection (HPI) were associated with increased risks of conventional adenomas (CAs), serrated polyps (SPs), non-adenomatous polyps (NAP), and colorectal cancer (CRC). Moderate to severe intestinal metaplasia specifically increased risks of NAP and CAs by 1.17-fold (95% CI 1.05-1.3) and 1.19-fold (95% CI 1.09-1.31), respectively. For CRC risk, low-grade intraepithelial neoplasia increased risk by 1.41-fold (95% CI 1.08-1.84), while high-grade intraepithelial neoplasia (OR 3.76, 95% CI 2.25-6.29) and gastric cancer (OR 4.81, 95% CI 3.25-7.09) showed strong associations. More advanced gastric pathology was correlated with progressively higher risks of CRC.

Conclusion

Precancerous gastric conditions are associated with increased colorectal neoplasm risk. Our findings can inform screening guidelines to target high-risk subgroups, advancing colorectal cancer prevention and reducing disease burden.
Case report: Successful treatment of advanced colon cancer in an eighty-year-old man with long-term and multi-stage endoscopic minimally invasive therapy
Authors: Zhang Nana , Zhu Lulu , Liu Yan , Chen Xiaolong , Zhang Bifang , Wen Chunhong , Zhang Huayu , Tang Qinglin , Zhang Mingqing
Published: February 2024

Background

No previous studies have reported on the use of minimally invasive endoscopic therapy for colon cancer in older patients.

Case presentation

An 80-year-old man was admitted to our hospital with haematochezia and diagnosed with advanced colon cancer in 2018. Traditional surgical care was rejected by his family. We successfully treated the patient with multiple minimally invasive endoscopic therapies, such as argon plasma coagulation, from 2018 to 2021.

Conclusion

Invasive endoscopic therapy is a feasible way to treat colon cancer in older patients.
Targeting SHMTs and MTHFDs in cancer: attractive opportunity for anti-tumor strategy
Authors: Zhang Xue , Wang Zhenhua
Published: February 2024

One-carbon metabolism is a universal metabolic process that mediates the transfer of one-carbon units for purine and thymidine synthesis. One-carbon metabolism has been found to be dysregulated in various cancer types due to its role in production of purine and pyrimidine nucleotides, epigenetic program, and redox homeostasis. One-carbon metabolism is composed a network of one-carbon metabolic enzymes. Disturbing the expression and enzymatic activity of these one-carbon metabolic enzymes could lead to fluctuations of metabolites in the tumor microenvironment. Serine hydroxymethyltransferases (SHMTs) and methylenetetrahydrofolate dehydrogenases (MTHFDs) are gradually recognized as important one-carbon metabolic enzymes for regulating tumor initiation and development, representing potential therapeutic targets for anti-tumor strategies. In the review, we primarily focused on the role of SHMTs and MTHFDs in cancer. Several inhibitors targeting MTHFDs and SHMTs have exert its potential to decrease tumor burden and inhibit tumor proliferation, highlighting the potential of targeting one-carbon metabolic enzymes for anti-cancer strategies.
The characteristics and operations of “online pharmacies” investigated in relation to medicines popularised during the coronavirus pandemic: a cross-sectional study
Authors: Oriakhi Oria Jason , Almomani Hamzeh , Patel Nilesh , Donyai Parastou
Published: February 2024

Aim: To explore the characteristics and operations of online pharmacies in relation to medications that gained widespread popularity and increased demand during the COVID-19 pandemic. Furthermore, to assess and compare practices between legitimate and “rogue” online pharmacies.

Methods: Fifteen COVID-19-pandemic-related medications were investigated through a UK-based online search. We systematically assessed the credibility of 116 retrieved online pharmacies using the factors: operational location, range of medicines sold, prescription requirements for Prescription Only Medicines (POMs), information exchange, payment/delivery, user-friendliness, legitimacy. Descriptive analysis was conducted, and legitimacy status (legitimate vs. illegitimate/rogue) was tested against relevant safety indicators using a chi-square test.

Results: Out of 116 “online pharmacies,” 55 (47%) were confirmed as “rogue,” 47 (41%) were verified as legitimate by the General Pharmaceutical Council (GPhC), and 14 (12%) were verified by other bodies but not by the GPhC. A total of 93 declared their “apparent” physical location of operation on the webpage of which 63 (67.7%, n = 93) declared a location that did not match their actual location according to the online pharmacy’s server (through their IP address). All 15 medicines analysed were readily available for purchase. A high percentage of online pharmacies offered POMs to the public (93.1%, n = 116). Only 23 out of the 116 online pharmacies assessed required a prescription for providing POMs, with only four of these verified as legitimate by the GPhC register, while most of the legitimate pharmacies (44 out of 47) offered online consultations as an alternative option instead of a prescription. Controlled medicines were offered by 28 online pharmacies 27 of which were deemed as rogue. Rogue online pharmacies were significantly more likely to guarantee refunds for medication, not require prescriptions for POMs, and not require an online consultation to obtain POMs.

Discussion: Findings reveal easy access to rogue online pharmacies, posing patient safety risks. We also found legitimate online pharmacies often offer online consultations without requiring prescriptions for POMs, raising concerns about inadequate safety checks. This emphasises the need for improved regulations for both types of online pharmacies, especially during public health crises.
Blood count, endocrine, immunologic, renal, and hepatic markers in a case-control animal study of induced periodontitis in female rodents
Authors: Estarreja João , Pimenta Ana Clara , Botelho João , Vilares Arminda Maria , Mendes José João , Rocha João , Pinto Rui , Mateus Vanessa , Machado Vanessa
Published: February 2024

Introduction: Periodontitis is a non-communicable chronic inflammatory disease with a systemic burden. Animal models of induced periodontitis help elucidate the mechanisms by which periodontal inflammation drives systemic effects. Studying this systemic involvement over longer follow-up periods may provide a strong foundation for future research on the association between diseases and periodontitis, particularly in female rats. Therefore, we aimed to compare blood, endocrine, immunologic, renal, and hepatic markers in a rat model of induced periodontitis in females with their control counterparts.

Methods: Experimental periodontitis was induced in 20 female Wistar rats by the application and maintenance of silk ligatures on the upper molars. The rats were then assessed for macroscopical analysis, complete blood count, and biochemical, endocrine, and immunologic markers at 21, 28, 42, and 56 days.

Results: Chronic periodontal inflammation was observed after 42 days of exposure to the ligatures. Additionally, it was also possible to notice significant systemic manifestations, such as the reduction of triiodothyronine and thyroxine levels, along with an increase in the expression of alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase.

Discussion: The study’s findings imply that certain changes can be underscored to highlight a reduced risk of conception. Notably, previous investigations have indicated that subfertile women exhibit lower levels of thyroid hormones and elevated lactate dehydrogenase expression. Despite the absence of preclinical data delineating a possible association between periodontitis and female infertility, the results of this study may prove to be a crucial contribution to both the scientific and medical fields.
Wolfberry genome database: integrated genomic datasets for studying molecular biology
Authors: Cao You-Long , Chen You-Yi , Li Yan-Long , Li Chung-I , Lin Shao-Ting , Lee Bing-Ru , Hsieh Chun-Lin , Hsiao Yu-Yun , Fan Yun-Fang , Luo Qing , Zhao Jian-Hua , Yin Yue , An Wei , Shi Zhi-Gang , Chow Chi-Nga , Chang Wen-Chi , Huang Chun-Lin , Chang Wei-Hung , Liu Zhong-Jian , Wu Wei-Sheng , Tsai Wen-Chieh
Published: February 2024

Wolfberry, also known as goji berry or Lycium barbarum, is a highly valued fruit with significant health benefits and nutritional value. For more efficient and comprehensive usage of published L. barbarum genomic data, we established the Wolfberry database. The utility of the Wolfberry Genome Database (WGDB) is highlighted through the Genome browser, which enables the user to explore the L. barbarum genome, browse specific chromosomes, and access gene sequences. Gene annotation features provide comprehensive information about gene functions, locations, expression profiles, pathway involvement, protein domains, and regulatory transcription factors. The transcriptome feature allows the user to explore gene expression patterns using transcripts per kilobase million (TPM) and fragments per kilobase per million mapped reads (FPKM) metrics. The Metabolism pathway page provides insights into metabolic pathways and the involvement of the selected genes. In addition to the database content, we also introduce six analysis tools developed for the WGDB. These tools offer functionalities for gene function prediction, nucleotide and amino acid BLAST analysis, protein domain analysis, GO annotation, and gene expression pattern analysis. The WGDB is freely accessible at https://cosbi7.ee.ncku.edu.tw/Wolfberry/. Overall, WGDB serves as a valuable resource for researchers interested in the genomics and transcriptomics of L. barbarum. Its user-friendly web interface and comprehensive data facilitate the exploration of gene functions, regulatory mechanisms, and metabolic pathways, ultimately contributing to a deeper understanding of wolfberry and its potential applications in agronomy and nutrition.
Combining transcranial magnetic stimulation with training to improve social cognition impairment in schizophrenia: a pilot randomized controlled trial
Authors: Vergallito Alessandra , Gramano Bianca , La Monica Kevin , Giuliani Luigi , Palumbo Davide , Gesi Camilla , Torriero Sara
Published: February 2024

Schizophrenia is a severe, chronic mental disorder that profoundly impacts patients’ everyday lives. The illness’s core features include positive and negative symptoms and cognitive impairments. In particular, deficits in the social cognition domain showed a tighter connection to patients’ everyday functioning than the other symptoms. Social remediation interventions have been developed, providing heterogeneous results considering the possibility of generalizing the acquired improvements in patients’ daily activities. In this pilot randomized controlled trial, we investigated the feasibility of combining fifteen daily cognitive and social training sessions with non-invasive brain stimulation to boost the effectiveness of the two interventions. We delivered intermittent theta burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC). Twenty-one patients were randomized into four groups, varying for the assigned stimulation condition (real vs. sham iTBS) and the type of cognitive intervention (training vs. no training). Clinical symptoms and social cognition tests were administered at five time points, i.e., before and after the treatment, and at three follow-ups at one, three, and six months after the treatments’ end. Preliminary data show a trend in improving the competence in managing emotion in participants performing the training. Conversely, no differences were found in pre and post-treatment scores for emotion recognition, theory of mind, and attribution of intentions scores. The iTBS intervention did not induce additional effects on individuals’ performance. The methodological approach’s novelty and limitations of the present study are discussed.
Resilience processes among Ukrainian youth preparing to build resilience with peers during the Ukraine-Russia war
Authors: Giordano Francesca , Lipscomb Shannon , Jefferies Philip , Kwon Kyong-Ah , Giammarchi Marianna
Published: February 2024

The war in Ukraine significantly impacts the mental health and well-being of its youth. Like other communities affected by war, Ukraine’s youth are at risk of developing psychopathological symptoms, and there is a shortage of mental health and psychosocial support services to address this. Resilience-building initiatives present an alternative approach to supporting the well-being of young people by promoting protective processes to enhance the likelihood of positive development in the context of adversity. Emerging research findings suggest that young people themselves can serve as powerful facilitators of such initiatives with one another. Yet, evidence about culturally and contextually relevant protective processes is needed to guide such interventions, especially among young people experiencing the war and working to boost resilience within their communities. In this study, we identified key protective processes Ukrainian youth depend on as they adapt to the conflict while also preparing to implement a resilience-building intervention as a facilitator. Through thematic analysis of transcripts of three training sessions with Ukrainian youth (n = 15, 100% female; aged 18–22), we identified the following themes: positive thinking, sense of control, emotion awareness and regulation, close personal relationships, and community support. Findings also highlighted the cultural and contextual nuance of these protective processes, as well as individual differences in the ways they co-occurred and manifested within each youth. Results have implications for developing tailored yet flexible resilience-building interventions that can be delivered by lay people, including youth with their peers, in Ukraine and other cultures and contexts.
Exposure to heavy metals and trace elements among pregnant women with twins: levels and association with twin growth discordance
Authors: Chen Lu , Zhao Wei , Zhao Li , Liang Qiongxin , Tang Jun , Zhou Weixiao , Zhang Yanhua , Wen Hong
Published: February 2024

Background

Twin growth discordance is one of the leading causes of perinatal mortality in twin pregnancies. Whether prenatal exposure to heavy metals and trace elements is associated with twin growth discordance has not been studied yet.

Objective

To evaluate the prenatal level of heavy metals and trace elements in twin pregnancy and its relationship with twin growth discordance.

Methods

This study involving 60 twin pairs and their mothers was conducted in Zhejiang Province, China, in 2020–2021. The concentration of heavy metals and trace elements in maternal blood, umbilical cord, and placenta were collected at delivery and measured by inductively coupled plasma tandem mass spectrometer. The association of prenatal level with twin growth discordance was evaluated using conditional logistic regression.

Results

High levels of heavy metal elements (thallium in maternal blood and umbilical cord blood of larger twins, vanadium in the placenta of larger twins) and trace elements (iodine in the placenta of larger twins) during pregnancy, as well as low levels of heavy metal elements (strontium in the umbilical cord blood of larger twins, strontium and chromium in the umbilical cord blood of smaller twins, strontium in the placenta of larger twins, molybdenum and lead in the placenta of smaller twins and difference of molybdenum in the placenta of twins), are associated with intertwin birthweight discordance. Univariate regression analyses showed a significant effect of gestational age at delivery and eleven trace element data on intertwin birthweight discordance. Multivariable logistic regression analysis with transformed variables as dichotomous risk factors combined with baseline demographic characteristics showed Tl in maternal blood as an independent risk factor. The model constructed by combining Tl in maternal blood (OR = 54.833, 95% CI, 3.839–83.156) with the gestational week (OR = 0.618, 95% CI, 0.463–0.824) had good predictive power for intertwin birthweight discordance (AUC = 0.871). The sensitivity analysis results indicate that the effect of maternal blood thallium on intertwin birthweight discordance is stable and reliable.

Conclusion

To our knowledge, ours is the first case–control study to investigate the association between elevated maternal thallium levels before delivery and twin growth discordance.
The impact of recreational cannabinoid legalization on utilization in a pregnant population
Authors: Torres Jacob , Miller Colton , Apostol Michael , Gross Jessica , Maxwell Jessie R.
Published: February 2024

Background

Marijuana potency and utilization both continue to increase across the United States. While the overall prevalence of cannabinoid utilization during pregnancy has been surveyed in various studies, the direct impact of changing governmental policies on pregnancy use is less characterized. Thus, we aimed to investigate how the legalization of recreational cannabinoid products impacted use during pregnancy in the state of New Mexico.

Methods

Participants who had a live birth during two study epochs were included: pre-legalization (Epoch 1: 1 January 2019–31 March 2021) and post-legalization (Epoch 2: 1 November 2021–30 November 2022). Participants were further divided into case group [prenatal cannabinoid exposure (PCE)] vs. control (no PCE), with cases being identified by documented self-report or a positive laboratory toxicology test for cannabinoid use during pregnancy.

Results

A total of 1,191 maternal/infant dyads were included in Epoch 1, and 378 maternal/infant dyads were included in Epoch 2. In Epoch 1, 788 dyads were controls with 403 cases, while Epoch 2 had 292 controls and 86 cases. Interestingly there was a significant decrease in self-report or positive laboratory toxicology tests in Epoch 2 compared to Epoch 1. Infants born following PCE in both Epoch groups were more commonly born via Cesarean section, had significantly smaller birth weight, length, and head circumference as well as significantly lower Apgar scores at 1 and 5 min.

Conclusion

The finding of decreased reported cannabinoid use in the post-legalization group is contradictory to previous studies which have shown increased rates of cannabinoid use after legalization. This could be due to multiple factors including changes in screening practices, the COVID-19 pandemic, and lack of commercialization of THC products. Additional studies are needed to further characterize how changing governmental policies impacts utilization during pregnancy.
The relationship between fat distribution and diabetes in US adults by race/ethnicity
Authors: Xu Furong , Earp Jacob E. , Riebe Deborah , Delmonico Matthew J. , Lofgren Ingrid E. , Greene Geoffrey W.
Published: February 2024

Introduction

This study examined the relationship between fat distribution and diabetes by sex-specific racial/ethnic groups.

Methods

A secondary data analysis of National Health and Nutrition Examination Survey 2011–2018 data (n = 11,972) was completed. Key variables examined were visceral adipose tissue area (VATA), subcutaneous fat area (SFA), diabetes prevalence, and race/ethnicity. The association of VATA and SFA and diabetes prevalence was examined separately and simultaneously using multiple logistic regression. Bonferroni corrections were applied to all multiple comparisons between racial/ethnic groups. All analyses were adjusted for demographics and muscle mass.

Results

VATA was positively associated with diabetes in both sexes (p < 0.001) and across all racial/ethnic groups (p < 0.05) except Black females. No statistically significant relationships were observed between SFA and diabetes while accounting for VATA with the exception of White females (p = 0.032). When comparing racial/ethnic groups, the relationship between VATA and diabetes was stronger in White and Hispanic females than in Black females (p < 0.005) while the relationship between SFA and diabetes did not differ between any racial/ethnic groups.

Conclusion

This study found that VATA is associated with diabetes for both sexes across almost all racial/ethnic groups independent of SFA whereas the only significant relationship between SFA and diabetes, independent of VATA, was observed in White females. The findings indicated that visceral fat was more strongly associated with diabetes than subcutaneous. Additionally, there are health disparities in sex-specific racial/ethnic groups thus further study is warranted.