bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy of scalp electroacupuncture combined with rehabilitation training for aphasia after head injury and its effect on patients’ language function and quality of life: An observational study
Authors: Li Lingzhe , Lu Yuexian , Huang Haiqiong , Ye Bihong , Mao Xianyu , Song Fengjun , Chen Yuanyuan
Published: June 2024

To explore the clinical efficacy of scalp electroacupuncture combined with rehabilitation training for aphasia after head injury, and analyze its effect on patients’ language function and quality of life. Our hospital randomly enrolled 100 aphasia patients caused by head injury treated from March 2020 to March 2022 as the experimental object and divided them into the control group and experimental group, with 50 cases in each group. The general rehabilitation training was performed to the control group and the scalp electroacupuncture combined with rehabilitation training was performed to the experimental group to compare their mini-mental state examination scores, communicative activities in daily living scores, aphasia battery of Chinese scores, quality of life scores, mental status scale in nonpsychiatric settings scores, National Institutes of Health Stroke Scale scores, effective rates, satisfaction of patients, and adverse reaction rates. In the between-group comparison, the patients in the experimental group had significantly higher mini-mental state examination scores, communicative activities in daily living scores, aphasia battery of Chinese scores, quality of life scores, effective rates, and satisfaction, and significantly lower mental status scale in nonpsychiatric settings scores, National Institutes of Health Stroke Scale scores and adverse reaction rates, which was statistically significant (P < .05 in all cases). The combination treatment of scalp electroacupuncture and rehabilitation training can effectively improve the language function and quality of life of patients with aphasia after head injury and remarkably enhance the treatment effect.
Focus on the effect of nursing care combined with cognitive intervention and functional training on negative emotion, compliance and quality of life in elderly patients with sudden deafness: A retrospective study
Authors: Zuo Yanlei , Yu Tao , Dong Zhi , Zhang Meng
Published: June 2024

To explore the effects of focused solution nursing combined with cognitive intervention combined with functional training on negative emotions, compliance and quality of life in elderly patients with sudden deafness. A total of 160 patients with sudden deafness in the elderly who were treated in our hospital from January 2019 to May 2021 were selected as the objects of this retrospective study. Based on different treatment approaches, subjects were divided into a control group and an observation group. Due to reasons such as the COVID-19 pandemic and transfers, 10 cases were lost to follow-up. In total, 75 cases were ultimately lost from both the control and observation groups. The control group implements cognitive intervention and functional training, and the observation group adopts focused solution nursing care on the basis of the control group. Observe and compare the effects of negative emotions, psychological distress, air conduction threshold level, compliance and quality of life of the 2 groups of patients. The air conduction hearing threshold level of the 2 groups of patients after nursing was lower than that before nursing and the observation group was lower than the control group. The positive coping scores of the 2 groups were significantly increased, and the negative coping scores were both significantly reduced and the observation group was in the 2 indicators. The degree of change was greater than that of the control group (P < .05). After nursing, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of the observation group were lower than those of the control group (P < .05). The mental vitality score, social interaction score, emotional restriction score, and mental status of the observation group were significantly higher than those of the control group. The observation group’s psychological compliance, activity compliance, dietary compliance, and treatment protocol compliance were significantly higher than those of the control group (P < .05). Adopting the focused solution model of nursing care can provide a better nursing recovery for elderly patients with sudden deafness, significantly improve the patient quality of life and anxiety and depression, improve patient compliance with treatment, and provide a certain reference for the nursing of elderly patients with sudden deafness.
Effect of care bundles based on importance degree analysis on postoperative comorbid state, coping style and disease management ability of patients with coronary heart disease
Authors: Wang Lihua , Zhou Bo , Wang Lijuan
Published: June 2024

Coronary heart disease (CHD) is a significant global health concern, particularly among the elderly. While care bundles present a comprehensive strategy for clinical disorders, their application in CHD rehabilitation remains understudied. This research addresses this gap by investigating the effectiveness of care bundles in CHD patients. By analyzing important performance degrees, we aim to contribute valuable insights to bridge existing knowledge deficiencies. Our study strives to establish a theoretical foundation for the broader implementation of care bundles, potentially improving the quality of care and patient outcomes in CHD rehabilitation. This is a retrospective study. 360 patients with CHD who were admitted to our hospital from January 2019 to October 2022 were enrolled in this retrospective study and divided into the observation group (n = 180) and control group (n = 180) according to the different care that they received. All cases were given routine nursing after CHD operation, and the observation group was given care bundles on the basis of the analysis of important performance degrees. The perioperative indexes, self-management ability score, depression, anxiety, stress scale (DASS), coping styles, medical compliance and the incidence of complications were compared between the 2 groups. Aftercare, the time of hospitalization and getting out-of-bed in the observation group was notably shorter (P < .05). Aftercare, the scores of self-management ability and related dimensions in the observation group were notably higher (P < .05). After care, the score of depression (P < .001), anxiety (P = .003) and stress (P = .017) of the observation group were notably lower. Aftercare, the observation group face score was significantly higher than the control group (P = .005), while the observation group avoidance score (P = .028) and yield score (P < .001) were significantly lower than the control group scores. Aftercare, the compliance behavior of patients in the observation group was notably better (P = .013). Aftercare, the incidence of complications in the observation group was notably lower (P = .039). Care bundles based on the degree of importance analysis can play a positive role in postoperative comorbid state, coping styles and self-management ability of patients with CHD, which can improve the rehabilitation effects on patients.
Efficacy and safety of 0.01% atropine combined with orthokeratology lens in delaying juvenile myopia: An observational study
Authors: Guo YanFang , Liu Ying , Hu ZhiWei , Li YueFeng , Zhang HePeng , Zhao SuYan
Published: June 2024

It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study, 172 adolescents aged 8 to 12 years who were admitted to the diopter department of Hengshui People Hospital from April 2021 to May 2022 were selected. According to the equivalent spherical diopter measured at the time of initial diagnosis, myopic patients were randomly divided into low myopia group (group A) and moderate myopia group (group B). At the same time, according to the different treatment methods, the patients were divided into the group wearing frame glasses alone (group c), the group wearing frame glasses with low-concentration Atropine (group d), the group wearing corneal shaping glasses alone at night (group e), and the group wearing corneal shaping glasses at night with low-concentration Atropine (group f). The control effect of myopia development and axial elongation in group f was better than that in groups d and e (P < .05). The effect of controlling myopia development and axial elongation in group f is with P > .05. The probability of postoperative adverse reactions in group f was lower and lower than that in the other groups. Low-concentration atropine combined with OK lens could effectively delay the development of juvenile myopia, and had a high safety. Low-concentration of Atropine would not have a significant impact on the basic tear secretion and tear film stability. Nightwear of OK lens also had no significant impact, but it would significantly reduce the tear film rupture time in the first 3 months, and at the same time, the tear film rupture time would be the same after 6 months as before treatment.
Various clinical manifestations of 223 patients with IgE deficiency in a tertiary hospital in China: A cross-sectional study
Authors: Zhang Junwu , Ni Jinyao , Kong Wanzhong , Liu Jinlin , Chen Yanxia
Published: June 2024

High Immunoglobulin E(IgE) levels associated with hypersensitivity or parasitic infection were well established, but the clinical significance of ultra-low IgE was largely unknown. Previous studies indicated these patients have an elevated risk of cancer, but large-scale epidemiological studies on the prevalence and clinical manifestations of these ultra-low IgE patients are still lacking. A total of 62,997 patients who were admitted to the First Affiliated Hospital of Wenzhou Medical University and had IgE level tests from January 2010 to March 2020 were included. Patients with serum IgE levels < 2 IU/mL were defined to have ultra-low IgE. And the clinical characteristics of these patients were retrospectively analyzed based on electronic medical record system and follow-up. A total of 223 patients (223/62,997, 0.35%) had ultra-low IgE were documented in 62,997 patients who had IgE tests. Among the clinical manifestations of these 223 ultra-low IgE patients, infection ranked first (125/223, 56.05%), following allergic diseases (51/223, 22.87%), hematological disorders (37/223, 16.59%), tumor (27/223, 12.11%) and autoimmune diseases (23/223, 10.31%). To the best of our knowledge, we first reported that the prevalence and clinical characteristics of 223 ultra-low IgE patients in China. The most common comorbidities were infection, allergic diseases, hematological disorders, tumor and autoimmune diseases.
Impact of resistance exercise program on muscle strength, cardiopulmonary function and glycolipid metabolism of bedridden population aged 80 years and above: A randomized controlled trial
Authors: Wang Yingjie , Huo Xiaopeng , Wang Xiaojing , Zhu Hongwei , Lai Xiaoxing , Yu Tong
Published: June 2024

Background:

This study aimed to evaluate the impact of a resistance exercise program in the bedridden older adults in China.

Methods:

The patients aged 80 years and above with stable diseases were randomly divided into control group (receiving routine treatment and nursing) and training group (receiving the elastic ball and elastic band training applied for 55 minutes, 3 times a week during 6 months).

Results:

A total of 59 patients (control group: 30; training groups: 29) completed the study. In terms of muscle strength, the patients of the training group had better grip strength and supine leg lifts and 30-s sit-to-stand actions. In terms of cardiopulmonary function and glycolipid metabolism, the patients in the training groups had better lung capacity and high-density lipoprotein.

Conclusion:

The low-load and low-intensity resistance training may effectively improve not only the muscle strength of the bedridden older adults, but also the lung function and blood lipid metabolism.
Elucidating causal relationships of diet-derived circulating antioxidants and the risk of non-scarring alopecia: A Mendelian randomization study
Authors: Ba Yuchen , Shen Lele , Peng Xiangning , Zhang Yujin , Wang Junwen
Published: June 2024

Previous observational studies revealed controversy about the effect of circulating antioxidants on risk of alopecia. In the present study, we investigated the causal relationships between diet-derived circulating antioxidants and 2 non-scarring alopecia using Mendelian randomization (MR). Instrumental variables for antioxidants (lycopene, retinol, ascorbate, β-carotene, α-tocopherol, and γ-tocopherol) were selected from published studies. Data for alopecia areata (AA) and androgenetic alopecia (AGA) was obtained from the FinnGen study project (R9 released in 2023), including 195 cases and 201,019 controls for AGA and 682 cases and 361,140 controls for AA. We used the inverse variance weighted method as the primary MR method. Three additional methods were used as sensitivity analysis to validate the robustness of the results. We found a causal relationship between absolute β-carotene levels and AGA risk (P = .039), but not with AA (P = .283). The results of Wald ratio showed a protective effect of absolute β-carotene levels against AGA, with per 0.1 ln-transformed β-carotene being associated with a 76% lower risk of AGA (OR: 0.24, 95% CI: 0.06–0.93). Based on the fixed effects inverse variance weighting results, we found that α-tocopherol was protective against both AGA (P = .026) and AA (P = .018). For each unit increase in α-tocopherol, the effects of change in AGA and AA were 0.02 (95% CI: 0.00–0.61) and 0.10 (95% CI: 0.01–0.67), respectively. The results did not reveal any other causal relationships. Our study identified 3 causal associations of antioxidants with the risk of non-scarring alopecia. These results provide new insights into the prevention of non-scarring alopecia through diet.
Mendelian randomization supports causality between COVID-19 and glaucoma
Authors: Chen Maolin , Zhang Yinhui , Yao Yu , Huang Yilan , Jiang Longyang
Published: June 2024

To determine whether there is a causal relationship between Corona Virus Disease 2019 (COVID-19) and glaucoma, a 2-sample Mendelian Randomization (MR) design was applied with the main analysis method of inverse-variance-weighted. The reliability of the results was checked using the heterogeneity test, pleiotropy test, and leave-one-out method. Four sets of instrumental variables (IVs) were used to investigate the causality between COVID-19 and glaucoma risk according to data from the IEU Genome Wide Association Study (GWAS). The results showed that 2 sets of COVID-19(RELEASE) were significantly associated with the risk of glaucoma [ID: ebi-a-GCST011071, OR (95% CI) = 1.227 (1.076–1.400),P = .002259; ID: ebi-a-GCST011073: OR (95% CI) = 1.164 (1.022–1.327),P = .022450; 2 sets of COVID-19 hospitalizations were significantly associated with the risk of glaucoma (ID: ebi-a-GCST011081, OR (95% CI) = 1.156 (1.033–1.292),P = .011342; ID: ebi-a-GCST011082: OR (95% CI) = 1.097 (1.007–1.196),P = .034908)]. The sensitivity of the results was acceptable (P > .05) for the 3 test methods. In conclusion, this MR analysis provides preliminary evidence of a potential causal relationship between COVID-19 and glaucoma.
A portent of catastrophic carbon dioxide embolism in laparoscopic hepatectomy: A case report
Authors: Li Mei , Yan Bing , Wang Mi , Zhu Shengmei , Kang Xianhui
Published: June 2024

Introduction:

Laparoscopic hepatectomy (LH) poses a high risk of carbon dioxide embolism due to extensive hepatic transection, long surgery duration, and dissection of the large hepatic veins or vena cava.

Patient concerns:

A 65-year-old man was scheduled to undergo LH. Following intraperitoneal carbon dioxide (CO2) insufflation and hepatic portal occlusion, the patient developed severe hemodynamic collapse accompanied by a decrease in the pulse oxygen saturation (SpO2).

Diagnosis:

Although a decrease in end-tidal carbon dioxide (ETCO2) was not observed, CO2 embolism was still suspected because of the symptoms.

Interventions and Outcomes:

The patient was successfully resuscitated after the immediate discontinuation of CO2 insufflation and inotrope administration. CO2 embolism must always be suspected during laparoscopic surgery whenever sudden hemodynamic collapse associated with decreased pulse oxygen saturation occurs, regardless of whether ETCO2 changes. Instant arterial blood gas analysis is imperative, and a significant difference between PaCO2 and ETCO2 is indicative of carbon dioxide embolism.

Conclusion:

Instant arterial blood gas analysis is imperative, and a significant difference between PaCO2 and ETCO2 is indicative of carbon dioxide embolism.
The prognostic value of preoperative laboratory data indicators in patients with esophageal carcinoma: An observational study
Authors: Ma Hui , Liu Yangchen , Ye Hongxun , Gao Fei , Li Zhu , Qin Songbing
Published: June 2024

Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) on overall survival (OS) in patients with esophageal carcinoma remains unclear. Thus, we examined these associations among patients with postoperative staged T3N0M0 esophageal carcinoma. The data of 246 patients with postoperative staged T3N0M0 esophageal carcinoma from January 1, 2010, to December 31, 2022, were retrospectively analyzed. OS was measured from the date of pathological diagnosis until either death or the last follow-up. The Kaplan–Meier method and multivariate Cox regression model were used to analyze the relationship between neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Platelet-to-lymphocyte ratio (LMR), SII, PNI, and OS. The predictive value of SII and PNI as a combined index was analyzed by the receiver operating characteristic curve (ROC). A total of 246 patients aged 65.5 ± 7.4 years were included in this study and 181 (73.6%) were male. The univariate analysis revealed that differentiation, vessel involvement, postoperative treatment, NLR, SII, PLR, LMR, PNI were predictors of OS (P < .05). After adjusted for potential confounds, multivariate Cox regression analysis showed that the differentiation, SII, PNI, and postoperative treatment were independent prognostic factors correlated with OS in patients with postoperative staged T3N0M0 esophageal carcinoma (P < .05). SII and PNI, as a combined indicator, have a higher predictive value for OS. The NLR, SII, PLR, LMR, and PNI could all be used as independent predictors of OS in patients with postoperative staged T3N0M0 esophageal carcinoma. The combination of SII and PNI can significantly improve the accuracy of prediction.
Transforming performance: The impact of an 8-week complex training program on strength, power, and change of direction in female basketball athletes
Authors: Wang Bin , Xie Enli , Liang Peigen , Liu Tianshu , Zhu Jian , Qin Guoyang , Su Xin
Published: June 2024

Background:

This study aimed to investigate the effect of complex training on the strength, power, and change of direction (COD) performance of college female basketball athletes.

Methods:

This design used experimental and randomized studies. A total of 32 female basketball players volunteered to participate in this study and were randomly allocated to a complex training group (CT group: n = 16) and a resistance training group (RT group: n = 16). The CT group performed CT and the RT group completed RT for 8 weeks. The CT and RT programs were developed based on the linear periodization theory, which required participants to train 2 times a week in the first 4 weeks and 3 times a week in the following 4 weeks. All participants were tested using the 5-0-5 COD test, Illinois agility test (IAT), one-repetition maximum back squat (1RM BS) test, and countermovement jump (CMJ) test before and after the 8-week training period.

Results:

Two-way repeated measure ANOVA showed a significant group × time interaction for the 5-0-5 COD, IAT, 1RM BS, and CMJ results after the intervention compared with that before the intervention (P < .05) in the CT group (effect size = 0.86–4.04). CT compared with RT caused remarkably larger enhancements in the IAT (P < .001) and CMJ (P = .040) scores.

Conclusion:

Our findings indicate that the implementation of CT could be a promising and innovative intervention for enhancing the strength, power, and COD performance of female basketball players.
Electroacupuncture for oculomotor nerve palsy after chemotherapy: A case report
Authors: Du Chun , Lu Chao , Li Guangliang , Deng Dehou , Chen Weiji
Published: June 2024

Introduction:

Oculomotor nerve palsy (ONP) is often discovered in the ophthalmology department, manifested as ptosis with the same side, eyeball in the fixed external booth, or accompanied by limited inward, upward, and downward movements. The present case report described the effect of electroacupuncture (EA) on a breast cancer patient with ONP after chemotherapy.

Patient concerns:

A 56-year-old breast cancer patient presented with severe ptosis and fixed right eye exotropia. Besides, it is challenging to perform the movement inward, upward, and downward, and with obvious diplopia.

Diagnoses:

The breast cancer patient was diagnosed with ONP, chemotherapy history.

Interventions:

The patient was introduced to acupuncture department to receiving EA treatment.

Outcomes:

After 12 times of EA treatments, the symptom of ptosis was significantly improved, and the right upper eyelid can lift autonomously as same as the left eye. Besides, the patient’s right lateral eye could move freely, and the symptoms of double vision disappeared.

Conclusion:

The case suggests that EA may be an effective alternative treatment for ONP.
Treating refractory thin endometrium through a novel way of activation and administration of Platelet-rich plasma in sexually active women: An interventional prospective cohort clinical study
Authors: Abbassi Rasha , Haddad Sultaneh , Haneyah Farah , Nakawa Wael , Murad Mohammed Subhi , Issa Abdulmoez Mohammed , Alkheder Ahmad , Azar Adel , dakhalalah bani hani Majd , Abbassi Haitham
Published: June 2024

A prospective cohort study investigated the effectiveness of platelet-rich plasma (PRP) infusion for refractory thin endometrium in 38 infertile patients. Patients showed significant improvement in endometrial thickness post-PRP injection, leading to successful implantation and pregnancy. The study revealed a negative correlation between antimullerian hormone (AMH) levels and the need for PRP interventions, suggesting higher ovarian reserve may reduce the necessity for repeated treatments. This implies AMH levels could serve as a prognostic indicator for treatment outcomes, aiding clinicians in optimizing protocols and reducing patient burden. Further research is needed to confirm these findings in larger and more diverse populations, along with exploring long-term reproductive success rates post-PRP treatment.
Malaria vaccination in Africa: A mini-review of challenges and opportunities
Authors: Olawade David B. , Wada Ojima Z. , Ezeagu Chiamaka Norah , Aderinto Nicholas , Balogun Malik A. , Asaolu Fiyinfoluwa T. , David-Olawade Aanuoluwapo Clement
Published: June 2024

Malaria remains an endemic public health concern in Africa, significantly contributing to morbidity and mortality rates. The inadequacies of traditional prevention measures, like integrated vector management and antimalarial drugs, have spurred efforts to strengthen the development and deployment of malaria vaccines. In addition to existing interventions like insecticide-treated bed nets and artemisinin-based combination therapies, malaria vaccine introduction and implementation in Africa could drastically reduce the disease burden and hasten steps toward malaria elimination. The malaria vaccine rollout is imminent as optimistic results from final clinical trials are anticipated. Thus, determining potential hurdles to malaria vaccine delivery and uptake in malaria-endemic regions of sub-Saharan Africa will enhance decisions and policymakers’ preparedness to facilitate efficient and equitable vaccine delivery. A multisectoral approach is recommended to increase funding and resources, active community engagement and participation, and the involvement of healthcare providers.
The syncope core management process in the emergency department: a consensus statement of the EUSEM syncope group
Authors: Möckel Martin , Catherine Janssens Kelly Ann , Pudasaini Samipa , Garcia-Castrillo Riesgo Luis , Moya Torrecilla Francisco , Golea Adela , Reed Matthew J. , Karamercan Mehmet , Fernández Cejas Juan Antonio , Laribi Said ,   on behalf of the EUSEM syncope group
Published: June 2024

The European Society of Cardiology issued updated syncope guidelines in 2018 which included recommendations for managing syncope in the emergency department (ED) setting. However, these guidelines lack detailed process-oriented instructions regarding the fact that ED syncope patients initially present with a transient loss of consciousness (TLOC), which can have a broad spectrum of causes. This study aims to establish a European consensus on the general process of the workup and care for patients with suspected syncope and provides rules for sufficient and systematic management of the broad group of syncope (initially presenting as TLOC) patients in the ED. A variety of European diagnostic and therapeutic standards for syncope patients were reviewed and summarized in three rounds of a modified Delphi process by the European Society for Emergency Medicine syncope group. Based on a consensus statement, a detailed process pathway is created. The primary outcome of this work is the presentation of a universal process pathway for the structured management of syncope patients in European EDs. The here presented extended event process chain (eEPC) summarizes and homogenizes the process management of European ED syncope patients. Additionally, an exemplary translation of the eEPC into a practice-based flowchart algorithm, which can be used as an example for practical use in the ED, is provided in this work. Syncope patients, initially presenting with TLOC, are common and pose challenges in the ED. Despite variations in process management across Europe, the development of a universally applicable syncope eEPC in the ED was successfully achieved. Key features of the consensus and eEPC include ruling out life-threatening causes, distinguishing syncope from nonsyncopal TLOCs, employing syncope risk stratification categories and based on this, making informed decisions regarding admission or discharge.
Caregiver greeting to infants under 6 months already reflects emerging differences in those later diagnosed with autism
Authors: Ford Aiden , Walum Hasse , Brice Beyonce , Patel Hely , Kunnikuru Sanjana , Jones Warren , Berman Gordon J. , Shultz Sarah
Published: June 2024

As infants develop, caregivers adjust their behaviour to scaffold their infant’s emerging skills, such that changes in infants’ social abilities are expected to elicit changes in caregiver behaviour. We examined whether changes in the probability of infant-directed caregiving behaviour—specifically, greeting, a ubiquitous signal used by caregivers to initiate reciprocal interactions—differ between infant–caregiver dyads with an infant later diagnosed with autism and dyads with a neurotypically developing infant during infants’ first 6 months. Using longitudinal data from 163 dyads, we found that caregivers in autism dyads (
n
= 40) used greeting less and at later infant ages than caregivers with a neurotypically developing infant (neurotypical dyads,
n
= 83). Caregivers in dyads with infants at elevated familial genetic likelihood for autism who did not receive an autism diagnosis (EL-non-autism dyads,
n
= 40) showed no differences in greeting compared with neurotypical dyads. Socioeconomic status partially mediated the difference between autism and neurotypical dyads. These findings show that autism and socioeconomic status were associated with the mutually adapted dynamics of dyadic interaction beginning in the first postnatal weeks. Importantly, differences in caregiver greeting observed in autism dyads are not interpreted as suboptimal behaviour from caregivers but rather indicate how early emerging social differences related to autism, years before overt features are present, may alter social learning opportunities elicited by the infant.
Integrative analysis reveals a macrophage-predominant, immunosuppressive immune microenvironment and subtype-specific therapeutic vulnerabilities in advanced salivary gland cancer
Authors: Zuljan Erika , von der Emde Benjamin , Piwonski Iris , Afonseca Pestana Ana Cristina , Klinghammer Konrad , Mock Andreas , Horak Peter , Heining Christoph , Klauschen Frederick , Pretzell Ina , Boerries Melanie , Brandts Christian H , Kreutzfeldt Simon , Teleanu Maria-Veronica , Hübschmann Daniel , Morris Luc G T , Keller Ulrich , Glimm Hanno , Fröhling Stefan , Ochsenreither Sebastian , Keilholz Ulrich , Blanc Eric , Beule Dieter , Rieke Damian T
Published: June 2024

Background

Salivary gland cancers (SGC) are rare and heterogeneous malignant tumors. Advanced SGC lack established treatment options and show poor response to immunotherapy. Here, an integrative multi-omics analysis in a large cohort of advanced SGC revealed insights into the tumor immune microenvironment (TIM) and distinct mechanisms of immune evasion.

Methods

A total of 104 patients with recurrent/metastatic SGC from the DKTK MASTER program were included in this study. Whole-exome or whole-genome sequencing and RNA-sequencing was performed on fresh frozen tumor tissue. The tumor immune microenvironment was analyzed using CIBERSORT deconvolution analysis and immune gene expression scores in bulk RNA-sequencing data. Single-nuclei sequencing and immunohistochemistry analyses were performed in selected samples. Results were validated in bulk RNA-sequencing data of a previously published independent dataset.

Results

Bulk transcriptome analysis revealed an immune-deserted TIM in the majority of advanced SGC samples. Immune exclusion was most prominent in adenoid cystic carcinoma (ACC) subgroup 1 exhibiting a downregulation of the antigen processing machinery. Only a small subset of advanced SGC, including few adenoid cystic carcinoma, exhibited T-cell inflammation, which was correlated with tumor mutational burden in Non-ACC samples. Subtype specific expression of immune checkpoints as well as cancer testis antigens were identified with prominent expression of VTCN1 in luminal cells within ACC. Single-cell RNA-sequencing and bulk RNA-seq deconvolution analysis validated immune cell exclusion and revealed a TIM that was dominated by M2 macrophages across SGC subtypes. Among evaluable patients treated with immune checkpoint inhibitors, a high T-cell to macrophage ratio was associated with clinical benefit.

Conclusions

These data support biomarker-based development of immune-checkpoint inhibition and the development of novel immune-checkpoint inhibitors and cellular therapies in SGC.

Trial Registration

Retrospectively registered,NCT05852522
DeepSEA: an alignment-free deep learning tool for functional annotation of antimicrobial resistance proteins
Authors: Borelli Tiago Cabral , Paschoal Alexandre Rossi , da Silva Ricardo Roberto
Published: June 2024

Surveying antimicrobial resistance (AMR) is essential to track its evolution and spread. Alignment-based annotation tools use strict identity (>80%) cutoffs to distinguish between non-resistant (NRP) and resistant proteins (ARP) only annotating proteins similar to those in their databases. Deep learning and Hidden Markov Models (HMM) based tools also depend on protein alignment at some level. DeepARG filters input data to select the um SNP ARG-like proteins and HMMs are built on multi-sequence alignment (MSA) specific for the protein in a given family or group. Therefore, there is a need to remove the alignment dependency of AMR annotation tools to identify proteins with remote homology Here we present DeepSEA, an alignment-free tool fitted on antimicrobial-resistant sets of aligned and unaligned ARPs and NRP. DeepSEA outperforms the current multi-class AMR classifiers DeepARG, RGI and AMRfinder. Furthermore, DeepSEA trained weights cluster AMR by resistant mechanisms, indicating that the model’s latent variables successfully captured distinguishing features of antibiotic resistance. Our tool annotated functionally validated tetracycline destructases (TDases) and confirmed the identification of a novel TDase found by HMM.
MYC and HSF1 Cooperate to Drive PLK1 inhibitor Sensitivity in High Grade Serous Ovarian Cancer
Authors: Williams Imade , DeHart Haddie , O’Malley Matthew , Walker Bobby , Ulhaskumar Vrushabh , Ray Haimanti , Delaney Joe R. , Nephew Kenneth P. , Carpenter Richard L.
Published: June 2024

Ovarian cancer is a deadly female cancer with high rates of recurrence. The primary treatment strategy for patients is platinum-based therapy regimens that almost universally develop resistance. Consequently, new therapeutic avenues are needed to overcome the plateau that current therapies have on patient outcomes. We describe a gene amplification involving both HSF1 and MYC, wherein these two genes on chromosome 8q are co-amplified in over 7% of human tumors that is enriched to over 30% of patients with ovarian cancer. We further found that HSF1 and MYC transcriptional activity is correlated in human tumors and ovarian cancer cell lines, suggesting they may cooperate in ovarian cancer cells. CUT&RUN for HSF1 and MYC in co-amplified ovarian cancer cells revealed that HSF1 and MYC have overlapping binding at a substantial number of locations throughout the genome where their binding peaks are near identical. Consistent with these data, a protein-protein interaction between HSF1 and MYC was detected in ovarian cancer cells, implying these two transcription factors have a molecular cooperation. Further supporting their cooperation, growth of HSF1-MYC co-amplified ovarian cancer cells were found to be dependent on both HSF1 and MYC. In an attempt to identify a therapeutic target that could take advantage of this dependency on both HSF1 and MYC, PLK1 was identified as being correlated with HSF1 and MYC in primary human tumor specimens, consistent with a previously established effect of PLK1 on HSF1 and MYC protein levels. Targeting PLK1 with the compound volasertib (BI-6727) revealed a greater than 200-fold increased potency of volasertib in HSF1-MYC co-amplified ovarian cancer cells compared to ovarian cancer cells wild-type HSF1 and MYC copy number, which extended to several growth assays, including spheroid growth. Volasertib, and other PLK1 inhibitors, have not shown great success in clinical trials and this study suggests that targeting PLK1 may be viable in a precision medicine approach using HSF1-MYC co-amplification as a biomarker for response.
Elevated phagocytic capacity directs innate spinal cord repair
Authors: Shaw Dana Klatt , Saraswathy Vishnu Muraleedharan , McAdow Anthony R. , Zhou Lili , Park Dongkook , Mote Ridim , Johnson Aaron N. , Mokalled Mayssa H.
Published: June 2024

Immune cells elicit a continuum of transcriptional and functional states after spinal cord injury (SCI). In mammals, inefficient debris clearance and chronic inflammation impede recovery and overshadow pro-regenerative immune functions. We found that, unlike mammals, zebrafish SCI elicits transient immune activation and efficient debris clearance, without causing chronic inflammation. Single-cell transcriptomics and inducible genetic ablation showed zebrafish macrophages are highly phagocytic and required for regeneration. Cross-species comparisons between zebrafish and mammalian macrophages identifiedtranscription and immune response regulator(tcim) as a macrophage-enriched zebrafish gene. Genetic deletion of zebrafishtcimimpairs phagocytosis and regeneration, causes aberrant and chronic immune activation, and can be rescued by transplanting wild-type immune precursors intotcimmutants. Conversely, genetic expression of humanTCIMaccelerates debris clearance and regeneration by reprogramming myeloid precursors into activated phagocytes. This study establishes a central requirement for elevated phagocytic capacity to achieve innate spinal cord repair.
Rickettsia β-peptide Reactivity with Immune IgM
Authors: Fuller Lee , Ordanza Susan , Reyna Julia
Published: June 2024

Spotted Fever Group (SFG) Rickettsia species maintain an s-layer with two major outer membrane proteins (OmpA and OmpB) aligned within a lipopolysaccharide (LPS) matrix external to the bacterial outer membrane. While the two typhus group species (R. typhi and R. prowazekii) maintain a similar s-layer containing only OmpB with its own specific form of LPS. A major component of these two types of OmpB is a specific and highly conserved beta peptide (β-peptide) non-covalently attached to the respective OmpB passenger domain. This β-peptide is initially translated as the c-terminus of the 168 kDa polypeptide and initially forms a membrane pore to allow the larger passenger domain to exit the bacterial cytoplasm through the outer membrane. Prior to the full exit of this passenger domain from the cytoplasm the long polypeptide chain is cleaved by a peptidase, leaving the c-terminus remaining as a beta-folded membrane pore and the N-terminal passenger domain exiting to the space between the bacterial membrane and the s-layer. The fate of this pore structure and the attachment of β-peptide to the OmpB continues to be examined and will be discussed as another protective component of the Rickettsia. An EIA IgM assay has been developed to utilize this antigen for clinical diagnostic use to accurately detect acute rickettsial infection in testing labs and lead to the availability of rapid test (lateral flow) formats for more immediate testing.
Protein-ligand co-design: a case for improving binding affinity between Type II NADH:quinone oxidoreductase and quinones
Authors: Porokhin Vladimir , Brown Anne M. , Hassoun Soha
Published: June 2024

Biological engineering aims to enhance biological systems by designing proteins with improved catalytic properties or ligands with enhanced function. Typically, applications permit designing proteins, e.g., an enzyme in a biodegradation reaction, or ligands e.g., a drug for a target receptor, but not both. Yet, some applications can benefit from a more flexible approach where both the protein and ligand can be designed or modified together to enhance a desired property. To meet the need for this co-design capability, we introduce a novel co-design paradigm and demon- strate its application to Ndh2-quinone pairings to enhance their binding affinity. Ndh2, type-II NADH dehydrogenase, is an enzyme found in certain bacteria that facilities extracellular electron transfer (EET) when interacting with exogenous quinone mediators. This interaction leads to the generation of a detectable electric current that can be used for biosensing applications. Our results demonstrate the benefits of the co-design paradigm in realizing Ndh2-quinone pairings with enhanced binding affinities, therefore highlighting the importance of considering protein-ligand engineering from a holistic co-design perspective.
Automatic sleep scoring for real-time monitoring and stimulation in individuals with and without sleep apnea
Authors: Esparza-Iaizzo Martín , Sierra-Torralba María , Klinzing Jens G , Minguez Javier , Montesano Luis , López-Larraz Eduardo
Published: June 2024

Digital therapeutics, enabled by advanced machine learning algorithms and medical wearable devices, offer a promising approach to streamline diagnostics and improve access to healthcare. Within this framework, automatic sleep scoring can provide accurate and efficient sleep analysis from electrophysiological signals recorded with wearable sensors, such as electroencephalography (EEG). However, the optimal configuration and temporal dynamics of automatic sleep scoring systems remain unclear, especially concerning their performance across different population samples. This study systematically investigates the impact of electrode setup, temporal scope, and population characteristics on the performance of automatic sleep scoring algorithms. Utilizing a convolutional neural network (CNN) model, we analyzed various electrode configurations and temporal dynamics using datasets comprising both healthy participants and individuals with sleep apnea. Our findings reveal that sleep scoring based on a single frontal EEG channel demonstrates reliable congruency with human expert scorers, with minimal improvement observed with additional sensors. Moreover, we demonstrate that real-time sleep scoring can be achieved with comparable accuracy to offline methods, which rely on past and future information to classify a window of interest. Remarkably, a notable reduction in decoding accuracy is observed for individuals with sleep disorders compared to healthy participants, highlighting the challenges inherent in accurately assessing sleep stages in clinical populations. Digital solutions for automatic sleep scoring hold promise for facilitating timely diagnoses and personalized treatment plans, with applications extending beyond sleep analysis to include closed-loop neurostimulation interventions. Our findings provide valuable insights into the complexities of automatic sleep scoring and offer considerations for the development of effective and efficient sleep assessment tools in both clinical and research settings.
ClpS directs degradation of primary N-end rule substrates inMycolicibacterium smegmatis
Authors: Presloid Christopher J. , Jiang Jialiu , Kandel Pratistha , Anderson Henry R. , Beardslee Patrick C. , Swayne Thomas M. , Schmitz Karl R.
Published: June 2024

Drug-resistant tuberculosis infections are a major threat to global public health. The essential mycobacterial ClpC1P1P2 protease has received attention as a prospective target for novel antibacterial therapeutics. However, efforts to probe its function in cells are constrained by our limited knowledge of its physiological proteolytic repertoire. Here, we interrogate the role of mycobacterial ClpS in directing N-end rule proteolysis by ClpC1P1P2 inMycolicibacterium smegmatis. Binding assays demonstrate that mycobacterial ClpS binds canonical primary N-degrons (Leu, Phe, Tyr, Trp) with moderate affinity. N-degron binding restricts the conformational flexibility of a loop adjacent to the ClpS N-degron binding pocket and strengthens ClpS•ClpC1 binding affinity ∼30-fold, providing a mechanism for cells to prioritize N-end rule proteolysis when substrates are abundant. Proteolytic reporter assays inM. smegmatisconfirm degradation of substrates bearing primary N-degrons, but suggest that secondary N-degrons are absence in mycobacteria. This work expands our understanding of the mycobacterial N-end rule pathway and identifies ClpS as a critical component for substrate specificity, providing insights that may support the development of improved Clp protease inhibitors.
An optimized method to visualize lipid droplets in brain tissue demonstrates their substantial accumulation in aged brains
Authors: Petrelli Francesco , Rey Alicia , Panfilova Diana , Madsen Sofia , Héritier Noéline , Knobloch Marlen
Published: June 2024

Lipid droplets (LDs) are cellular stores for lipids. These organelles have recently gained interest in neuroscience because they accumulate in various cell types in neurodegenerative diseases. However, their role under physiological conditions is still not fully understood. Classical LD staining methods, which use lipophilic dyes like BODIPY 493/503 (BD493) or antibodies against LD coat proteins, show very few LDs in healthy brain tissue. Our recently developed novel endogenous LD reporter mouse challenges this view. We have been able to detect numerous LDs in healthy brain tissue from both adult and developing mice without staining. To understand why classical staining and endogenous labeling yield different results, we thoroughly investigated the effects of tissue preparation and detergent used in LD detection. We found that BD493 works poorly in brain tissue, while other lipophilic dyes visualize many LDs. We also found that antibody-based LD detection depends on tissue pretreatment and detergent concentration but can reveal a similar number of LDs as observed with the endogenous LD reporter mouse. Taken together, we here present an optimized procedure for LD detection in brain tissue using commercially available dyes and antibodies. Using these methods, we demonstrate that LDs are numerous in healthy brain tissue and substantially accumulate in aged brains in various cell types, including neurons.
Contribution of neurons that expressfruitlessandClocktranscription factors to behavioral rhythms and courtship
Authors: Deluca Anthony , Bascom Brooke , Key Planas Daniela A , Kocher Matthew A , Torres Marielise , Arbeitman Michelle N
Published: June 2024

Animals need to integrate information across neuronal networks that direct reproductive behaviors and circadian rhythms. In Drosophila, the master regulatory transcription factors that direct courtship behaviors and circadian rhythms are co-expressed in a small set of neurons. In this study we investigate the role of these neurons in both males and females. We find sex-differences in the number of thesefruitlessandClock-expressing neurons (fru∩Clkneurons) that is regulated by male-specific Fru. We assign thefru∩Clkneurons to the electron microscopy connectome that provides high resolution structural information. We also discover sex-differences in the number offru-expressing neurons that are post-synaptic targets ofClk-expressing neurons, with more post-synaptic targets in males. Whenfru∩Clkneurons are activated or silenced, males have a shorter period length. Activation offru∩Clkneurons also changes the rate a courtship behavior is performed. We find that activation and silencingfru∩Clkneurons impacts the molecular clock in the sLNv master pacemaker neurons, in a cell-nonautonomous manner. These results reveal how neurons that subserve the two processes, reproduction and circadian rhythms, can impact behavioral outcomes in a sex-specific manner.