bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging to monitor disease activity in giant cell arteritis treated with ultra-short glucocorticoids and tocilizumab
Authors: Christ Lisa , Bonel Harald M , Cullmann Jennifer L , Seitz Luca , Bütikofer Lukas , Wagner Franca , Villiger Peter M
Published: July 2024

Objectives

MRI is well established for diagnosing GCA. Its role in monitoring disease activity has yet to be determined. We investigated vascular and musculoskeletal inflammation using MRI in the patients of the GUSTO trial to assess the utility of MRI in monitoring disease activity.

Methods

Eighteen patients with newly diagnosed GCA received 500 mg methylprednisolone intravenously for three consecutive days followed by tocilizumab monotherapy from day 3 until week 52. Cranial, thoracic and abdominal MRI exams were performed at baseline (active, new-onset disease), and at weeks 24, 52 (remission on-treatment) and 104 (remission off-treatment). MRI findings typical for PMR as well as extent and severity of vasculitic disease were rated.

Results

In total, 673 vascular segments and 943 musculoskeletal regions in 55 thoracic/abdominal MRI and 490 vascular segments in 49 cranial MRI scans of 18 patients were analysed. Vasculitic vessels were still detectable in one in four cranial segments at week 24. At weeks 52 and 104, no cranial vascular segment showed a vasculitic manifestation. Large vessels, except for the ascending aorta, and PMR displayed little or no decrease in inflammatory findings over time.

Conclusion

Vasculitic manifestations in the cranial vessels normalized after 52 weeks of treatment, whereas large vessel and PMR findings persisted despite lasting full remission. The dynamics of cranial vessel signals suggest that MRI of these arteries might qualify as a potential diagnostic tool for monitoring disease activity and for detecting relapse after 52 weeks of treatment.
Immunosuppressives discontinuation after renal response in lupus nephritis: predictors of flares, time to withdrawal and long-term outcomes
Authors: Panagiotopoulos Alexandros , Kapsia Eleni , Michelakis Ioannis El , Boletis John , Marinaki Smaragdi , Sfikakis Petros P , Tektonidou Maria G
Published: July 2024

Objectives

The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients.

Methods

Data from 137 inception cohort LN patients were analysed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models.

Results

IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) [odds ratio (OR): 1.07, P = 0.046] and higher SLEDAI-2K at tapering initiation (OR: 2.57, P = 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (≥2/3 of follow-up) (OR: 0.28, P = 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR: 1.70, P = 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% estimated glomerular filtration rate decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median 124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, P < 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in the entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (β = −19.8, P = 0.014).

Conclusion

Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavourable long-term outcomes. Earlier IS D/C is feasible in membranous LN.
Reasons for Discharge in a National Network of Early Psychosis Intervention Programs
Authors: Phalen Peter L , Smith William R , Jones Nev , Reznik Samantha J , Marti C Nathan , Cosgrove John , Lopez Molly , Calkins Monica E , Bennett Melanie E
Published: July 2024

Background

Discharge from early psychosis intervention is a critical stage of treatment that may occur for a variety of reasons. This study characterizes reasons for discharge among participants in early psychosis intervention programs participating in the Early Psychosis Intervention Network (EPINET) which comprises >100 programs in the United States organized under 8 academic hubs.

Study Design

We analyzed 1787 discharges, focusing on program completion, unilateral termination by the client/family, and lost contact with the client/family. We performed exploratory analyses of demographic, clinical, and functional predictors of discharge reason. Variables predictive of discharge type were included in multilevel logistic regressions, allowing for the estimation of predictors of discharge reason and variability in rates by program and hub.

Study Results

An estimated 20%–30% of enrolled patients completed the program. Program completion rates were higher among participants who were older on admission, had lower negative symptoms severity, spent more time in education, employment, or training, and who were covered by private insurance (a close proxy for socioeconomic status). Programs were more likely to lose contact with male participants, Black participants, and participants who were never covered by private insurance. After accounting for patient-level factors, there was substantial program-level variation in all 3 discharge outcomes, and hub-level variability in the proportion of participants who completed the program. The impact of race on program completion varied substantially by program.

Conclusions

Participants were discharged from early psychosis intervention services for diverse reasons, some of which were associated with sociocultural factors. Disengagement is a widespread problem affecting all hubs.
A narrative review of mechanisms linking romantic relationship experiences to sleep quality
Authors: Xie Yuxi , Feeney Brooke C
Published: July 2024

Although a significant body of research has revealed associations between romantic relationship experiences and sleep quality, there has not been clarity regarding the mechanisms underlying such associations. Toward this end, we review the existing studies that have tested mechanisms linking romantic relationship experiences to sleep quality. Guided by both theory and existing research, we organize our review around five key categories of mechanisms that may explain associations between romantic relationship experiences and sleep quality: emotional/affective responses, self-perceptions, social perceptions, self-regulation, and biological functioning. Our review of the literature indicates strong evidence in support of the mediating effects of emotional/affective mechanisms (e.g. emotions and mood states) in explaining associations between various aspects of romantic relationships (e.g. relationship satisfaction, partner conflicts, and attachment orientation) and sleep quality. Although there is ample theoretical support for the other mechanisms proposed, and although all proposed mechanisms have been separately linked to both romantic relationship experiences and sleep quality, few studies have directly tested them, pointing to profitable directions for future research. Understanding underlying mechanisms will enable the development of wise, process-based interventions that target specific mechanisms to improve couple members’ sleep quality and romantic relationship functioning.
An analysis of the influence of preslaughter management factors on welfare and meat quality outcomes in fed beef cattle in the United States
Authors: Davis Melissa K , Sullivan Paxton A , Hess Ann M , Nair Mahesh N , Mooney Daniel F , Edwards-Callaway Lily N
Published: July 2024

During the preslaughter phase, cattle are transported from their place of origin to a slaughter facility, experiencing transportation, lairage, environmental factors, and novel environments. Although research exists that has focused how the preslaughter phase impacts cattle welfare and meat quality, some significant preslaughter management factors and subsequent welfare and meat quality outcomes have not been thoroughly explored. The objective of this study was to assess the effects of preslaughter management factors on welfare and meat quality outcomes in fed beef cattle in the United States. Transportation factors, environmental characteristics, lairage factors, cattle characteristics, and several meat quality variables were collected from 5 federally inspected commercial processing facilities in the United States. After excluding slaughter lots that included <75% complete datasets, a total of 619 slaughter lots representing 84,508 head of cattle were used for further analysis. Predictor variables of interest included processing plant, cattle breed, sex class, operation shift at the plant, distance traveled to the plant, truck waiting time to unload at the plant, lairage duration and space allowance, temperature humidity index, and windspeed. Outcome variables of interest included cattle mobility, carcass bruising, dark cutting (DC), quality grades, and hot carcass weights. Logistic and linear regressions were used to analyze the associations between the predictor and outcome variables of interest. Increased distance traveled and truck waiting time were associated with higher odds of mobility impairment (P = 0.0009 and P = 0.007, respectively), with each 10 km increase in distance traveled having an odds ratio (OR) of 1.001 (95% confidence interval [CI]: 1.000 to 1.001) and each 1-min increase in waiting time having an OR of 1.003 (CI: 1.001 to 1.004). Conversely, a 10-km increase in distance traveled decreased the odds of carcass bruising (OR: 0.997, CI: 0.996 to 0.998; P < 0.0001). Longer lairage was associated with increased odds of DC (P = 0.0415), with each 60-min increase in duration having an OR of 1.034 (CI: 1.001 to 1.068). The results demonstrate the importance of truck arrival management (i.e., scheduling, prioritizing unloading) on mobility. Focusing on lairage management (i.e., density and time) may provide some opportunities to improve meat quality.
Impact of extreme pre-monsoon drought on xylogenesis and intra-annual radial increments of two tree species in a tropical montane evergreen broad-leaved forest, southwest China
Authors: Liu Ya-Nan , Fan Ze-Xin , Lin You-Xing , Kaewmano Arisa , Wei Xiao-Lian , Fu Pei-Li , Grießinger Jussi , Bräuning Achim
Published: July 2024

Tropical montane evergreen broad-leaved forests cover the majority of forest areas and have high carbon storage in Xishuangbanna, southwest China. However, stem radial growth dynamics and their correlations with climate factors have never been analyzed in this forest type. By combining bi-weekly microcoring and high-resolution dendrometer measurements, we monitored xylogenesis and stem radius variations of the deciduous species Betula alnoides Buch.-Ham. ex D. Don and the evergreen species Schima wallichii (DC.) Korth. We analyzed the relationships between weekly climate variables prior to sampling and the enlarging zone width or wall-thickening zone width, as well as weekly radial increments and climate factors during two consecutive years (2020 to 2021) showing contrasting hydrothermal conditions in the pre-monsoon season. In the year 2020, which was characterized by a warmer and drier pre-monsoon season, the onset of xylogenesis and radial increments of B. alnoides and S. wallichii were delayed by three months and one month, respectively, compared with the year 2021. In 2020, xylem formation and radial increments were significantly reduced for B. alnoides, but not for S. wallichii. The thickness of enlarging zone and wall-thickening zone in S. wallichii were positively correlated with relative humidity, and minimum and mean air temperature, but were negatively correlated with vapor pressure deficit during 2020 to 2021. The radial increments of both species showed significant positive correlations with precipitation and relative humidity, and negative correlations with vapor pressure deficit and maximum air temperature during two years. Our findings reveal that drier pre-monsoon conditions strongly delay growth initiation and reduce stem radial growth, providing deep insights to understand tree growth and carbon sequestration potential in tropical forests under a predicted increase in frequent drought events.
Evaluation of neck ultrasound measurements as a difficult airway predictor: A prospective observational study
Authors: Çinar Köse Elif Özge , Tekin Murat , Cesur Sevim , Çam İsa , Baykara Zehra Nur
Published: July 2024

This study aimed to investigate the relationship between cervical measurements and difficult airways using ultrasonographic measurements. American Society of Anesthesiologists grade I to III, male or female, 120 adult patients, undergoing elective surgery were enrolled in the study. The study involved measuring the distance of the trachea, cricoid cartilage, thyroid cartilage, vocal cord anterior commissure, and hyoid bone to the skin using a 10 to 13 MHz linear ultrasound probe in the transverse plane. Additionally, the length of the cricothyroid and thyrohyoid membranes, along with their distance from the skin, were measured using the probe in the sagittal plane. Subsequently, another experienced anesthesiologist conducted mask ventilation and intubation after the patient’s induction of general anesthesia. Throughout this process, the patient was assessed for difficulties in mask ventilation, laryngoscopy, and intubation. 28 (23.3%) patients had a difficult airway. Analyzing the measurements associated with difficult airways, the most reliable predictor was the epiglottis midline-skin distance [AUC (area under the curve): 0.847, P < .001, cutoff: >19.9, sensitivity: 78.6%, specificity: 79.4%]. Additionally, other factors such as hyoid bone to skin distance, thyroid cartilage to skin distance, thyrohyoid membrane to skin distance, and vocal cord anterior commissure-skin distance were also identified as predictors for a difficult airway. The increase in the distance of the epiglottis midline, vocal cord anterior commissure, hyoid bone, thyrohyoid membrane, and thyroid cartilage to the skin at the level of the isthmus measured by ultrasonography is predictive of difficult airways. Based on our study outcomes, we assert that ultrasonographic evaluation can be used in the prediction of difficult airways.
Morvan’s syndrome with hypercoagulable condition in a patient positive for anti-CASPR2 antibodies: A case report
Authors: Pang Xintong , Li Yanming , Liu Zining , Mao Yafei , Li Xinyuan , Gao Lingling , Geng Yulan , Meng Li
Published: July 2024

Rationale:

The phenomenon of hypercoagulability has not been previously documented in individuals with Morvan’s syndrome, especially in those associated with contactin-associated protein-like receptor 2 (CASPR2).

Patient concerns:

A previously healthy 32-year-old Chinese male was admitted to the hospital with central and peripheral neurologic symptoms. The patient was tested positive for anti-CASPR2 antibodies, and also presented with an activated coagulation state on admission, characterized by a low activated partial thromboplastin time and a high platelet count. With gradual improvement of clinical symptoms, activated partial thromboplastin time, and platelet count returned to normal. Simultaneously, anti-CASPR2 antibody titers significantly decreased and eventually became undetectable.

Diagnoses:

The patient was diagnosed as Morvan’s syndrome with positive anti-CASPAR2 antibodies accompanied with hypercoagulable state.

Interventions:

Plasmapheresis was administered to improve the symptoms combined with prednisolone acetate therapy.

Outcomes:

The patient experienced complete resolution of all symptoms during hospitalization and generally recovery after 2 months of discharge.

Lessons:

Emphasis should be directed towards hypercoagulability in individuals diagnosed with Morvan’s syndrome, particularly those presenting with positive anti-CASPR2 antibodies. Anticoagulant therapy may represent a novel therapeutic approach for individuals afflicted with Morvan’s syndrome and exhibiting positivity for anti-CASPR2 antibodies.
Acupuncture for constipation in Parkinson’s disease: A systematic review and meta-analysis of randomized controlled trials
Authors: Li Zhao , Niu Qun , Yang Kai , Zhao Keni , Yin Shao , Zhu Fengya
Published: July 2024

Background:

Parkinson’s disease (PD) is the second most common neurological disease worldwide, and there is a potential interaction between PD and constipation. PD constipation often causes significant trouble for patients and seriously affects their quality of life. Acupuncture is widely used for treating constipation and has been clinically proven. However, it is unclear whether the current evidence is sufficient to support acupuncture to improve PD constipation.

Methods:

We searched the Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Wan Fang Data Knowledge Service Platform, and Chinese Scientific Journal Database (VIP database) for randomized controlled trials from inception through July 1, 2023. Randomized controlled trials (RCTs) included acupuncture, sham acupuncture, and medication for PD constipation. Stata 16.0 software and Cochrane RoB2.0 were used for data processing and migration risk analysis.

Results:

The 11 studies included a total of 960 patients. The results showed that acupuncture or acupuncture combined with conventional treatment seemed to have advantages in improving complete spontaneous bowel movements (WMD: 1.49, 95% CI: 0.86, 2.11; P < .00001), Patient-Assessment of Constipation Quality of Life questionnaire (WMD: −11.83, 95% CI: −15.67, −7.99; P < .00001), the chronic constipation severity scale (CCS) (SMD: −0.99, 95% CI: −1.40, −0.58; P < .01), and c(RRP) (WMD: 2.13, 95% CI: 0.44, 3.82; P < .05).

Conclusion:

The present results show that compared with conventional treatment, acupuncture combined with conventional treatment seems to increase the number of spontaneous defecations in PD patients, improve quality of life, increase rectal resting pressure, and alleviate the severity of chronic constipation. Thus, acupuncture has the potential to treat PD constipation. However, due to the study’s limitations, higher-quality RCTs are needed for verification.
Prognostic value and immune infiltration of the NEK family in clear cell renal cell carcinoma
Authors: Zhu Yingli , Lin Jianfan , Li Yufei , Luo Zuojie
Published: July 2024

Clear cell renal cell carcinoma (ccRCC) is a fatal urological malignancy. Members of the never-in mitosis gene A (NIMA)-related kinase (NEK) family have been found to participate in the progression of several cancers and could be used as target genes to treat corresponding diseases. Nonetheless, the prognostic value and immune infiltration levels of NEK family genes in ccRCC remain unknown. The GSCA, TIMER, and GEPIA databases were utilized to examine the differential expression of NEK family members in ccRCC, and the Kaplan–Meier plotter was utilized to analyze the prognosis. The STRING database was used to construct a protein-protein interaction network. Analysis of function was performed by the Sangerbox tool. In addition, the relationship between NEK family genes and immune cells was explored using the TIMER and TISIDB databases. Finally, we used quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) for experimental verification. Transcriptional levels of NEK2, NEK3, NEK5, NEK6, and NEK11 significantly differed between ccRCC and normal tissues. Moreover, there was a significant correlation between NEK1, NEK2, NEK4, NEK8, NEK9, and NEK10 and their clinicopathological stages in patients with ccRCC. Based on survival analysis, ccRCC patients with high transcriptional levels of NEK2, NEK3, NEK8, and NEK10 and low transcriptional levels of NEK1, NEK4, NEK5, NEK6, NEK7, NEK9, NEK11 had shorter survival times. Additionally, a significant relationship was observed between NEK family members and immune cell infiltration, immune cell markers, and immune subtypes. These results indicate that NEK family members are significantly differentially expressed in ccRCC, and a significant correlation exists between the NEK family and prognosis and immune infiltration. NEK family members may act as therapeutic targets and prognostic indicators in ccRCC.
Incidence of seizures in ICU patients with diffuse encephalopathy and its predictors
Authors: Alkhotani Amal M , Al sulaimi Jwana Faisal , Bana Afaf Ali , Abu Alela Hanadi
Published: July 2024

Encephalopathy is a diffuse brain dysfunction that results from systemic disorder. Patients with diffuse encephalopathy are at risk of developing clinical and electrographic seizures. The aim of this study is to assess the prevalence of electrographic seizures in a setting of encephalopathy and the clinical and electroencephalogram predictors. We retrospectively reviewed all continuous electroencephalograms done between 2019 and 2022. Continuous electroencephalograms with diffuse encephalopathy were included in the study. A total of 128 patients with diffuse encephalopathy were included in this study. Patients’ ages ranged from 18 to 96 years old with a mean age of 55.3 ± 19.2 years old. Nine out of 128 patients had seizures with an incidence of 7%. Sixty-six point six percent were nonconvulsive electrographic seizures. Fourteen point three percent of the female patients with diffuse encephalopathy had seizures as compared to none of the male patients (P = .002). Also, 12% of patients with a history of epilepsy experienced seizures versus 5.8% of patients without this history (P = .049). Among electrographic features, 25% of patients with delta background had seizures versus 2.3% of the other patients (P = .048). Likewise, 90% of patients with periodic discharges developed seizures in comparison with none of the patients without (P = .001). Seizures are seen in 7% of patients with diffuse encephalopathy. Female gender, past history of epilepsy, delta background and periodic discharges are significant predictors of seizure development in patients with diffuse encephalopathy.
Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ
Authors: Park Jisun , Joo Eun Young , Yoo Myung Ji , Kim Su-Jin , Jang Woori , Lee Ji-Eun
Published: July 2024

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.
Evaluating the effect of green tea intake on cardiovascular diseases: A Mendelian randomization study in European and East Asian populations
Authors: Liang Qiaoli , Peng Ziming
Published: July 2024

Previous research shows that more than 70% of cardiovascular diseases (CVDs) are attributed to modifiable risk factors. Here, we investigated relationship between consumption of green tea in European and East Asian populations and risk of CVDs using Mendelian randomization (MR). Instrumental variables for green tea intake were obtained from genome-wide association studies (GWASs) of 64,949 Europeans and 152,653 East Asians. GWASs for CVDs were derived from UK BioBank and BioBank Japan projects. The main method selected for MR analysis was either the inverse variance weighted (IVW) or Wald ratio, depending on the quantity of single nucleotide polymorphisms. Furthermore, we performed sensitivity analyses to confirm the reliability of the findings. Based on the results of IVW, there is no causal relationship between consumption of green tea and risk of 4 CVDs among Europeans (atrial fibrillation: OR = 1.000, 95% CI: 0.995–1.005, P = .910; heart failure: OR = 1.003, 95% CI: 0.994–1.012, P = .542; ischemic stroke: OR = 1.002, 95% CI: 0.993–1.011, P = .690; coronary artery disease: OR = 1.001, 95% CI: 0.996–1.007, P = .677). Sensitivity analyses and supplementary MR analyses also verify the robustness of the findings. Likewise, there was no correlation between the consumption of green tea and the occurrence of CVDs in East Asians. The consumption of green tea is not associated with a reduced risk of CVDs in populations from Europe and East Asia. This means that those who are trying to reduce their risk of CVDs by drinking more green tea may not benefit from doing so.
Olverembatinib combined with inotuzumab ozogamicin in relapsed refractory Philadelphia chromosome-positive acute lymphoblastic leukemia: A case report
Authors: Liu Tong , Wang Chang , Fu Yu , Yang Yan-ping , Tan Ye-hui
Published: July 2024

Rationale:

Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival.

Patient concerns:

A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review.

Diagnoses:

Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation.

Interventions:

Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease.

Outcomes:

The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy.

Lessons:

The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.
The prognostic significance of CD117-positive mast cells and microvessel density in colorectal cancer
Authors: Bolat Kucukzeybek Betul , Dere Yelda , Akder Sari Aysegul , Ocal Irfan , Avcu Emel , Dere Ozcan , Orgen Calli Aylin , Dinckal Cigdem , Tunakan Mine , Kucukzeybek Yuksel
Published: July 2024

The prognostic significance of angiogenesis has been demonstrated in various types of cancer. However, in colorectal cancer (CRC), there are conflicting results regarding the relationship between angiogenesis and clinical-histopathological prognostic factors. Mast cells are immune system cells found in the inflammatory microenvironment; their role in carcinogenesis and prognosis remains unclear although they are considered to cause cancer development and progression. The present study aims to evaluate the prognostic significance of mast cell accumulation and angiogenesis assessed by microvessel density (MVD) in patients with CRC. Patients who underwent curative resection and who were not treated with neoadjuvant chemotherapy were included. The anti-CD34 antibody and anti-CD117 antibody were utilized for the immunohistochemical assessment of MVD and the mast cell count (MCC) in the tissue samples, respectively. The relationship between MCC, MVD, survival and clinical-histopathological prognostic factors were evaluated. A total of 94 patients were enrolled to the study. In a median 49-month follow-up, 65 patients (69.1%) died. The 5-year disease-free survival was 61.1% and 31.3% for the group with CD34 < 18.3% and CD34 > 18.3%, respectively (P = .001). The same groups presented 5-year overall survival rates of 77, 1% and 51, 4%, respectively (P, .012). The MVD was found to be associated with the pathological T stage, lymph node metastasis and distant metastasis (P < .05). Although the MCC was positively correlated with MVD, there was no association between the MCC and clinical-histopathological prognostic factors. MVD-assessed angiogenesis was significantly related to survival and the clinical-histopathological prognostic factors in patients diagnosed with CRC.
Prognostic analysis of anoikis-related genes in bladder cancer: An observational study
Authors: Huang Fu , Zhou Liquan , Sun Junjie , Ma Xihua , Pei Yongfeng , Zhang Qiuwen , Yu Yanqing , He Guining , Zhu Lirong , Li Haibin , Wang Xiaoming , Long Fuzhi , Huang Haipeng , Zhang Jiange , Sun Xuyong
Published: July 2024

Anoikis is proved to play a crucial role in the development of cancers. However, the impact of anoikis on the prognosis of bladder cancer (BLCA) is currently unknown. Thus, this study aimed to find potential effect of anoikis in BLCA. The Cancer Genome Atlas (TCGA)-BLCA and GSE13507 cohorts were downloaded from TCGA and the Gene Expression Omnibus (GEO) databases, respectively. Differentially expressed genes (DEGs) were screened between BLCA and normal groups, which intersected with anoikis-related genes to yield anoikis-related DEGs (AR DEGs). Univariate COX, rbsurv, and multivariate COX analyses were adopted in order to build a prognostic risk model. The differences of risk score in the different clinical subgroups and the relevance between survival rate and clinical characteristics were explored as well. Finally, chemotherapy drug sensitivity in different risk groups was analyzed. In total, 78 AR DEGs were acquired and a prognostic signature was build based on the 6 characteristic genes (CALR, FASN, CSPG4, HGF, INHBB, SATB1), where the patients of low-risk group had longer survival time. The survival rate of BLCA patients was significantly differential in different groups of age, stage, smoking history, pathologic-T, and pathologic-N. The IC50 of 56 drugs showed significant differences between 2 risk groups, such as imatinib, docetaxel, and dasatinib. At last, the results of real time quantitative-polymerase chain reaction (RT-qPCR) demonstrated that the expression trend of CALR, HGF, and INHBB was consistent with the result obtained previously based on public databases. Taken together, this study identified 6 anoikis-related characteristic genes (CALR, FASN, CSPG4, HGF, INHBB, SATB1) for the prognosis of BLCA patients, providing a scientific reference for further research on BLCA.
Safety of TNF-α inhibitors: A real-world study based on the US FDA Adverse Event Reporting System Database
Authors: Zheng Bohui , Liu Manting , Dai Dandan , Shang Yifan , Dou Xiangyun , Liu Bingshuo , Zhong Zilan , Huang Shulan , Luo Dongqiang
Published: July 2024

As a common treatment for rheumatoid arthritis (RA), the adverse reactions of TNF-α inhibitors (TNFis) in practical application have garnered attention. This study aims to investigate the adverse drug events (ADEs) associated with TNFi in RA patients as reported in the FDA Adverse Event Reporting System, to offer insights for clinical use. Cases related to RA and primarily involving TNFi were extracted from the FDA Adverse Event Reporting System database and compared by gender stratification. Screening was conducted based on reporting odds ratio and information component to identify positive ADEs for different TNFis and evaluate common and unique ADEs among various TNFis. There are 4 common ADEs among TNFis, including pulmonary tuberculosis, infection, hypersensitivity, and herpes zoster, as described in the package inserts. However, each TNFi has unique positive ADEs. Adalimumab has 63 unique positive ADEs, including lower respiratory tract inflammation, systemic lupus erythematosus rash, vascular dementia, ovarian neoplasm, adhesion, sarcoma, coccidioidomycosis, etc. Golimumab has 6 unique positive ADEs, including pneumonia cryptococcal, device deployment issue, pneumonia bacterial, polyneuropathy, device malfunction, device issue, etc; certolizumab has 24 unique positive ADEs, including maternal exposure before pregnancy, premature rupture of membranes, exposure via breast milk, staphylococcal sepsis, erysipelas, low birth weight baby, herpes virus infection, premature delivery, etc; etanercept has 180 unique positive ADEs, including joint destruction, chondrolysis, finger deformity, ankle deformity, joint warmth, etc; infliximab has 60 unique positive ADEs, including Hodgkin’s disease, metastatic neoplasm, non-Hodgkin’s Lymphoma, etc. Although the aforementioned 5 TNFis share common ADEs such as herpes zoster, clinicians must exercise caution when selecting specific medications, especially for RA patients concurrently suffering from malignancies. The analysis indicates that infliximab is associated with 60 unique positive ADEs, including Hodgkin’s disease, metastatic neoplasm, and non-Hodgkin’s lymphoma; therefore, these patients should use infliximab with greater caution. Similarly, certolizumab should be used with increased caution in pregnant and postpartum women.
Influence of patient safety perception and attitude on inpatients’ willingness to participate in patient safety: An observation study
Authors: Won Mi Hwa , Hwang In Suk , Shin Sun-Hwa
Published: July 2024

Patient safety (PS) in clinical settings focuses primarily on ensuring active patient participation. However, there is limited understanding of patients’ willingness to participate. This study aimed to investigate the association between PS perception, attitude, and inpatients’ willingness to participate in PS. This cross-sectional study was conducted with 295 inpatients admitted to a tertiary hospital in South Korea between May and July 2023. Structured questionnaires were used to collect the data. The collected data were subjected to various analytical techniques including descriptive statistics, t tests, Pearson correlation analysis, and multiple regression analysis. Willingness to participate in PS of inpatients showed a statistically significant difference in PS education experience (t = −2.69, P = .008). There was a significant positive correlation between PS perception and attitude (r = .54, P < .001). Additionally, willingness to participate in PS had significant positive correlations with PS perception (r = .62, P < .001) and PS attitude (r = .48, P < .001). The factors influencing willingness to participate in PS were PS perception (β = .51, P < .001) and attitude (β = .20, P < .001). Based on these research findings, it is important to provide inpatients with education and campaigns to improve their perceptions and attitudes toward PS. In addition, it is essential to develop programs that encourage and support patient engagement in PS in hospitals. These efforts will promote active implementation of PS activities by inpatients in clinical settings.
Gut microbiota and epigenetic choreography: Implications for human health: A review
Authors: Kim Bailee , Song Angel , Son Andrew , Shin Yonghwan
Published: July 2024

The interwoven relationship between gut microbiota and the epigenetic landscape constitutes a pivotal axis in understanding human health and disease. Governed by a myriad of dietary, genetic, and environmental influences, the gut microbiota orchestrates a sophisticated metabolic interplay, shaping nutrient utilization, immune responses, and defenses against pathogens. Recent strides in genomics and metabolomics have shed light on the intricate connections between these microbial influencers and the host’s physiological dynamics, presenting a dynamic panorama across diverse disease spectra. DNA methylation and histone modifications, as key players in epigenetics, intricately align with the dynamic orchestration of the gut microbiota. This seamless collaboration, notably evident in conditions like inflammatory bowel disease and obesity, has captured the attention of researchers, prompting an exploration of its nuanced choreography. Nevertheless, challenges abound. Analyzing data is intricate due to the multifaceted nature of the gut microbiota and the limitations of current analytical methods. This underscores the need for a multidisciplinary approach, where diverse disciplines converge to pave innovative research pathways. The integration of insights from microbiome and epigenome studies assumes paramount importance in unraveling the complexities of this intricate partnership. Deciphering the synchronized interactions within this collaboration offers a deeper understanding of these delicate interplays, potentially heralding revolutionary strides in treatment modalities and strategies for enhancing public health.
Altered resting-state brain entropy (BEN) by rTMS across the human cortex
Authors: Song Dong-Hui , Deng Xin-Ping , Shang Yuan-Qi , Chang Da , Wang Ze
Published: July 2024

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method effective in treating various neuropsychiatric disorders, yet its mechanisms are not fully understood. In general, rTMS protocols are categorized into excitatory protocols including high-frequency rTMS (HF-rTMS) and intermittent theta burst stimulation (iTBS), and inhibitory protocols including low-frequency rTMS (LF-rTMS) and continuous theta burst stimulation (cTBS). Brain entropy (BEN) measures irregularity, disorders, and complexity of brain activity, our previous studies have indicated that BEN affects excitatory rTMS, including HF-rTMS and iTBS. However, two important questions remain whether rTMS is equally sensitive to inhibitory rTMS and whether it can induce opposite brain activities, another question concerns whether rTMS can induce specific changes across brain regions. To address these issues, we utilized our own cTBS targeted on the left dorsal lateral prefrontal cortex (L-DLPFC) dataset and publicly available LF-rTMS dataset with stimulating sites including the L-DLPFC, left temporal parietal junction (L-TPJ), and left occipital cortex (L-OCC), from the OpenNeuro. BEN maps were calculated before and after stimulation. The results showed that L-DLPFC cTBS increased BEN in the MOFC and L-DLPFC LF-rTMS increased BEN in the MOFC, subgenual anterior cingulate cortex (MOFC/sgACC) and putamen, the regions are consistent with our previous findings with HF-rTMS and iTBS. Additionally, L-TPJ LF-rTMS resulted in increased BEN in the right TPJ, while L-OCC LF-rTMS led to decreased BEN in the posterior cingulate cortex (PCC). Our findings suggest that BEN is not only sensitive to excitatory rTMS but also to inhibitory rTMS. Moreover, LF-rTMS induces different effects across brain regions, as detected by BEN.
Wearable facemask-attached disposable printed sensor arrays for point-of-need monitoring of ammonia in breath
Authors: Barandun Giandrin , Sanli Abdulkadir , Yap Chun Lin , Collins Alexander Silva Pinto , Grell Max , Kasimatis Michael , Levy Jeremy B. , Güder Firat
Published: July 2024

Blood sampling, despite its historical significance in clinical diagnostics, poses challenges such as invasiveness, infection risks, and limited temporal fidelity for continuous monitoring. In contrast, exhaled breath offers a non-invasive, pain-free, and continuous sampling method, carrying biochemical information through volatile compounds like ammonia (NH3). NH3 in exhaled breath, influenced by kidney function, emerges as a promising biomarker for renal health assessment, particularly in resource-limited settings lacking extensive healthcare infrastructure. Current analytical methods for breath ammonia, though effective, often face practical limitations. In this work, we introduce a low-cost, internet-connected, paper-based wearable device for measuring exhaled ammonia, designed for early detection of kidney dysfunction at the point-of-need. The device, which attaches to disposable facemasks, utilizes a disposable paper-based sensor array housed in a biodegradable plastic enclosure to mitigate high relative humidity (RH) issues in breath analysis. We validated our technology using a laboratory setup and human subjects who consumed ammonium chloride-containing candy to simulate elevated breath ammonia. Our wearable sensor offers a promising solution for rapid, point-of-need kidney dysfunction screening, particularly valuable in resource-limited settings. This approach has potential applications beyond kidney health monitoring, including chemical industry safety and environmental sensing, paving the way for accessible, continuous health monitoring.
Thyroid hormones maintain parvalbumin neuron functions in mouse neocortex
Authors: Ren Juan , Markossian Suzy , Guyot Romain , Aubert Denise , Li Dongdong , Cauli Bruno , Riet Fabrice , Wong Jiemin , Flamant Frédéric , Richard Sabine
Published: July 2024

Parvalbumin-expressing (PV) GABAergic interneurons play a key role in maintaining the excitation-inhibition balance in the mammalian neocortex. Here we address the function of thyroid hormones in PV neurons in the mouse neocortex. To this end, Cre/loxP recombination system was used to express a dominant negative mutated receptor of thyroid hormones only in PV neurons. We analyzed the neocortical phenotype of these mice, in which thyroid hormone signaling is eliminated specifically in PV neurons, by combining genomics, histology, electrophysiology, and behavioral analysis. We found significantly altered gene expression, reduced expression of key perineuronal net components, reduced PV neuron excitability, behavioral hyperactivity and increased susceptibility to seizures. These results highlight that thyroid hormones are not only required for the differentiation of PV interneurons, but also for the maintenance of their inhibitory function after the onset of parvalbumin expression.
Neural dynamics underlying minute-timescale persistent behavior in the human brain
Authors: Courellis Hristos S. , Valiante Taufik A. , Mamelak Adam N. , Adolphs Ralph , Rutishauser Ueli
Published: July 2024

The ability to pursue long-term goals relies on a representations of task context that can both be maintained over long periods of time and switched flexibly when goals change. Little is known about the neural substrate for such minute-scale maintenance of task sets. Utilizing recordings in neurosurgical patients, we examined how groups of neurons in the human medial frontal cortex and hippocampus represent task contexts. When cued explicitly, task context was encoded in both brain areas and changed rapidly at task boundaries. Hippocampus exhibited a temporally dynamic code with fast decorrelation over time, preventing cross-temporal generalization. Medial frontal cortex exhibited a static code that decorrelated slowly, allowing generalization across minutes of time. When task context needed to be inferred as a latent variable, hippocampus encoded task context with a static code. These findings reveal two possible regimes for encoding minute-scale task-context representations that were engaged differently based on task demands.
Gibberellic acid and light effects on seed germination in the seagrassZostera marina
Authors: Pieraccini Riccardo , Whatley Lawrence , Koedam Nico , Dierick Jasper , Vanreusel Ann , Dolch Tobias , Van der Stocken Tom
Published: July 2024

Seagrass meadows have been heavily affected by human activities, withZostera marinabeing one of the most impacted species. Seed-based methods are currently the preferred approach for their restoration. However, low germination rates and seedling establishment often affect the success rate and feasibility of restoration projects.

We tested, for the first time, the combined effect of light spectra (white and red light and darkness), photoperiod, and gibberellic acid (GA3) on seed germination rates inZ. marina, by means of an incubation experiment with a fully crossed design, employing penalised logistic regression and Cox proportional hazards analysis. Seedling development was subsequently monitored to assess the potential side-effects of the priming agents on morphometric growth.

Light priming positively affects germination, with germination probability being substantially increased when red light and darkness treatments were combined with GA3. Time to germination was reduced at mid- to high- GA3concentrations. Morphometric analysis of the cotyledonary and leaf tissue development did not indicatea posterioriside-effects of seed priming on growth.

Light and GA3priming favour germination probability and release from dormancy inZ. marinaseeds. Seed priming can reduce stress- or manipulation-induced dormancy and can be considered in contexts where on-demand germination is required.
Beyond Auditory Relay: Dissecting the Inferior Colliculus’s Role in Sensory Prediction, Reward Prediction and Cognitive Decision-Making
Authors: Du Xinyu , Xu Haoxuan , Song Peirun , Zhai Yuying , Ye Hangting , Bao Xuehui , Huang Qianyue , Tanigawa Hisashi , Tu Zhiyi , Chen Pei , Zhao Xuan , Rauschecker Josef P. , Yu Xiongjie
Published: July 2024

The Inferior Colliculus (IC) has traditionally been regarded as an important relay in the auditory pathway, primarily involved in relaying auditory information from the brainstem to the thalamus. However, this study uncovers the multifaceted role of the IC in bridging auditory processing, sensory prediction, and reward prediction. Through extracellular recordings in monkeys engaged in a sound duration-based deviation detection task, we observed a “climbing effect” in neuronal firing rates, indicative of an enhanced response over sound sequences linked to sensory prediction rather than reward anticipation. Moreover, our findings demonstrate reward prediction errors within the IC, highlighting its complex integration in auditory and reward processing. Further analysis revealed a direct correlation between IC neuronal activity and behavioral choices, suggesting its involvement in decision-making processes. This research highlights a more complex role for the IC than traditionally understood, showcasing its integral role in cognitive and sensory processing and emphasizing its importance in integrated brain functions.