bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between successful weaning from nasogastric tube feeding and thoracic muscle mass in patients with aspiration pneumonia
Authors: Lee Hyun Woo , Kim Dong Hyun , Jin Kwang Nam , Lee Hyo-Jin , Lee Jung-Kyu , Park Tae Yeon , Kim Deog Kyeom , Heo Eun Young
Published: October 2023

Nasogastric tube feeding is often used to provide optimal nutrition and hydration in patients with aspiration pneumonia. However, evidence regarding radiologic indicators for successful nasogastric tube weaning is lacking. We investigated whether thoracic skeletal muscle assessment can be useful for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia. This longitudinal, observational study included subjects with aspiration pneumonia who underwent a videofluoroscopic swallowing study (VFSS) and chest computed tomography (CT) in Boramae Medical Center, from January 2012 to December 2019. We estimated the area under the receiver operating characteristics curve (AUC) to evaluate the predictive performance of skeletal muscle and visceral fat parameters and VFSS results for successful weaning from nasogastric tube feeding. A board-certified radiologist measured muscle and fat areas. Muscle and fat volumes were segmented and measured using an externally validated convolutional neural network model. Among the 146 included patients, nasogastric tube feeding was successfully transitioned to oral feeding in 46.6%. After adjusting for covariables related to successful weaning, skeletal muscle areas, indices, and volume indices were positively associated with successful nasogastric tube weaning. Although VFSS results and skeletal muscle parameters alone showed suboptimal performance for predicting successful weaning, a prediction model combining skeletal muscle index at the T4 level and VFSS results improved the prediction performance to an acceptable level (AUC ≥ 0.7). Skeletal muscle index measured at the T4 level may be a useful supplementary indicator for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia.
Root canal treatment of a six-canal first mandibular molar with extensive periapical lesion: A case report
Authors: Li Xin , Sun Shuyu , Zheng Tengyi
Published: October 2023

Rationale:

There is an increasing tendency for case reports to reveal anatomical aberrances in mandibular first molars, such as the lateral and accessory canals. Thus, clinicians should pay special attention to anatomic variances when dealing with mandibular first molars requiring endodontic treatment to prevent reinfection within the root canal system, which is responsible for the failure of root canal treatment.

Patient concerns:

This article presents the clinical report and successful root canal treatment of a 24-year-old healthy female patient with an extensive periapical lesion in a 6-canal first mandibular molar. The patient was admitted to the endodontic department because of a periapical abscess found 1 month ago in her left mandibular first molar.

Diagnosis:

Chronic apical periodontitis was diagnosed based on clinical examination coupled with radiographic and cone-beam computed tomography images.

Interventions:

The treatment plan was to first perform root canal therapy and then perform clinical observation.

Outcomes:

During 1-year follow-up period, the treated tooth was asymptomatic, and complete resolution of the extensive apical lesion was eventually achieved, as shown in the postoperative cone-beam computed tomography images and clinical examination.

Lessons:

The present case emphasizes the importance of a comprehensive understanding of root canal morphology, especially rare anatomical variations, to ensure successful root canal treatment. Additionally, the case report adds to the library of previously reported cases of extensive periapical lesions with a direct connection to the root canal system, which demonstrates the potential clinical advantages of root canal therapy as a conservative nonsurgical approach in these cases.
Metachronous double primary malignant tumors with nasopharyngeal carcinoma and diffuse malignant peritoneal mesothelioma accompanied with paraneoplastic syndromes treated with nivolumab: A case report
Authors: Tang Liang-Ke , Li Zhi-Ke , Xiang Ya-Lang , Ma Dai-Yuan , Du Guo-Bo
Published: October 2023

Rationale:

Multiple primary malignant tumors are rare and challenging to diagnose. Diffuse malignant peritoneal mesothelioma (DMPM) originate from the peritoneum, which lacks specific clinical manifestations and is difficult to diagnose, with a short survival about 10 to 13 months for inoperable ones. This is the first report of metachronous double primary malignant tumors in nasopharyngeal carcinoma and DMPM accompanied with paraneoplastic syndromes.

Patient concerns:

A 61-year-old man presented with abdominal discomfort with a history of nasopharyngeal carcinoma 5 years ago.

Diagnoses:

The diagnosis of DMPM was finally confirmed by laparoscopic mesenteric biopsies. Paraneoplastic syndromes including increased platelets were present when diagnosis, followed by increased neutrophils after disease progression.

Interventions:

Due to intolerable for surgery, he was treated with pemetrexed combined with nivolumab, intraperitoneal infusion of nivolumab, radiotherapy, anlotinib and maintenance treatment of nivolumab.

Outcomes:

Progression-free survival in first line is 12 months, overall survival is 23 months.

Lessons:

This indicate that comprehensive treatment including immunotherapy may be helpful for inoperable DMPM patients with nasopharyngeal carcinoma accompanied with paraneoplastic syndromes.
The level of ratio between matrix metalloproteinase-1 (MMP-1) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) after prolotherapy intervention and the functional outcome in patient with frozen shoulder: A randomized controlled trial
Authors: Sam Nuralam , Yusuf Irawan , Idris Irfan , Adnan Endy , Haryadi Ratna Darjanti , Hamid Firdaus , Usman Andry , Johan Muhammad Phetrus , Zainuddin Andi Alfian , Bukhari Agussalim
Published: October 2023

Objective:

To determine the effect of prolotherapy on functional outcome changes, along with ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor matrix metalloproteinase-1 (TIMP-1) as an indicator of tissue repair in the glenohumeral joint in frozen shoulder patients.

Design:

Single-blinded randomized controlled trial.

Subjects/Patients:

Participants with frozen shoulder.

Methods:

The prolotherapy group is the study group, and the normal saline (NS) group is the control group. Each group was given injections at weeks 0, 2, 4, and 6. Level of biomarker levels was measured at week 6 and week 12 after there. Functional outcomes were measured at weeks 0, 6, and 12.

Results:

A significant difference in week 6 and week 12 was demonstrated in the ratio of MMP-1/TIMP-1 level between the prolotherapy group and the normal saline group (P value = .002). Both groups performed well regarding the Numerical Rating Scale score and functional outcome. Compared to the normal saline group, prolotherapy changed the mean range of motion in flexion and internal rotation.

Conclusion:

Prolotherapy is considered to play a role in repairing cartilage based on biomarker assessment, particularly the ratio of MMP-1/TIMP-1—prolotherapy effectiveness in improving functional outcome and Numerical Rating Scale score.
Efficacy of donepezil plus hydrogen–oxygen mixture inhalation for treatment of patients with Alzheimer disease: A retrospective study
Authors: Dan Zhaojun , Li Haifeng , Xie Jin
Published: October 2023

To investigate the clinical effect of donepezil combined with hydrogen–oxygen mixture inhalation in the treatment of patients with Alzheimer disease (AD), a total of 273 AD patients admitted to our hospital from March 2018 to March 2022 were retrospectively analyzed and assigned into an observation group (n = 138) and a control group (n = 135) according to the different treatment that they received. The control group was treated with donepezil tablets, while the observation group was treated with donepezil tablets combined with hydrogen–oxygen mixture inhalation. The scores of mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer’s Disease Assessment Scale-Cognition, activity of daily living scale (ADL) and the P300 event-related potential were compared between the 2 groups. After treatment, MMSE score, MoCA score, and ADL score in both groups increased after treatment (P < .01), while the improvement in the observation group was more significant than that in the control group (P < .001 for MMSE, P = .003 for MoCA, and P = .013 for ADL). The scores of Alzheimer’s Disease Assessment Scale-Cognition in the observation group decreased after treatment (P < .05), while the improvement in the observation group was more significant than that in the control group (P = .005). After treatment, the latency of P300 in both groups was shortened (P < .01), and the improvement in the observation group was more significant than that in the control group (P < .001). The amplitude of the observation group increased after treatment (P < .01), and the improvement of the observation group was significant than that of the control group (P = .007). The clinical efficacy of donepezil combined with hydrogen–oxygen mixture inhalation in the treatment of AD is better than that of donepezil alone, which is worthy of further study.
Severe hemolytic disease of the newborn caused by JKb antibody: Two case reports and literature review
Authors: Jiang Liang-Liang , Bi Shao-Hua , Yu Jing , Zhao Feng-Xia , Teng Maggie , Teng Ru-Jeng
Published: October 2023

Background:

JKb antibody rarely causes severe hemolytic disease in the newborn except in 1 case, required blood exchange transfusion but later died of intractable seizure and renal failure. Here we describe 2 cases of JKb-induced severe neonatal jaundice requiring blood exchange transfusion with good neurological outcome.

Case presentation:

Two female Chinese, ethnic Han, term infants with severe jaundice were transferred to us at the age of 5- and 4-day with a total bilirubin of 30.9 and 25.9 mg/dL while reticulocyte counts were 3.2% and 2.2%, respectively. Both infants were not the firstborn to their corresponding mothers. Direct and indirect Coombs’ tests were positive, and JKb antibody titers were 1:64 (+) for both mothers. Phototherapy was immediately administered, and a blood exchange transfusion was performed within 5 hours of admission. Magnet resonance image showed no evidence of bilirubin-induced brain damage, and no abnormal neurological finding was detected at 6 months of life.

Conclusion:

JKb antibody-induced hemolytic disease of the newborn usually leads to a benign course, but severe jaundice requiring blood exchange transfusion may occur. Our cases suggest good outcomes can be achieved in this minor blood group-induced hemolytic disease of the newborn if identified and managed early enough.
Epidemiological survey of hypertension among middle-aged and elderly adults in Anhui Province
Authors: Zhai Yujia , Cui Can , Yu Tianyun , Su Zengfeng
Published: October 2023

To understand and analyze the prevalence and treatment of hypertension among residents aged 45 years and older in northern and southern Anhui Province to provide an opportunity to improve awareness, taking into account and standardizing hypertension management. Using a stratified cluster random sampling method, Anhui Province was divided into northern and southern Anhui regions using the Yangtze River as the boundary. The prevalence rate, awareness rate, treatment rate, control rate, related risk factors and complications of hypertension in the community population aged ≥ 45 years in Anhui Province were investigated using a questionnaire survey and a physical examination. The chi-square test was used to analyze the regional differences in hypertension prevalence, awareness, treatment and control rates. Weighted logistic regression was used to analyze the risk factors for hypertension. A total of 1331 residents aged ≥ 45 years were included. The results showed that the overall prevalence of hypertension in the Anhui Province population aged ≥ 45 years was 47.48% (50.73% in northern Anhui and 43.21% in southern Anhui), and the prevalence of hypertension in northern Anhui was higher than that in southern Anhui. The survey showed that the overall hypertension awareness rate in Anhui Province was 59.67%, the hypertension treatment rate was 44.46%, and the hypertension control rate was 30.70%. The differences between the 2 regions was statistically significant. The hypertension awareness, treatment and control rates in southern Anhui were higher than those in northern Anhui (P < .05). The risk factors for hypertension were older age, rural residence, male, obesity, low education level, high salt diet, smoking, excessive drinking, poor sleep, insufficient exercise, a family history of hypertension, a history of diabetes, and a history of hyperlipidemia. The most common complication of hypertension in middle-aged and elderly people in Anhui Province was cerebrovascular disease, followed by cardiovascular disease. Calcium channel blockers were the most commonly used antihypertensive drugs in middle-aged and elderly people in Anhui Province, followed by angiotensin converting enzyme inhibitor or angiotensin receptor blocker receptor antagonists.
SYNPO2 upregulation is an unfavorable prognostic factor for nasopharyngeal carcinoma patients
Authors: Chang Shih-Lun , Yang Ching-Chieh , Lai Hong-Yue , Tsai Hsin-Hwa , Yeh Cheng-Fa , Lee Sung-Wei , Kuo Yu-Hsuan , Kang Nai-Wen , Wu Wen-Bin , Chen Tzu-Ju
Published: October 2023

Nasopharyngeal carcinoma (NPC) is the most common malignant neoplasm of the nasopharynx. Despite improvements in the clinical treatment strategies for NPC, NPC patients usually have poor survival rates because of late diagnosis, tumor metastasis, and recurrence. Therefore, the identification of potential diagnostic and prognostic markers for NPC is imperative. We investigated the differential expression of cell adhesion-related genes (gene ontology:0003779) and tumorigenesis-related genes (GSE12452) in patients with NPC. The correlations between synaptopodin-2 (SYNPO2) immune expression and clinicopathological features were analyzed using Pearson chi-square test. Multivariate analysis was performed using Cox proportional hazards model. SYNPO2 expression was significantly higher in NPC tumor tissues than in nontumor tissues. High SYNPO2 expression was significantly associated with the advanced disease stage (P = .006). Univariate analysis showed that high expression of SYNPO2 was associated with poor disease-specific survival, distal metastasis-free survival, and local recurrence-free survival in patients with NPC. Notably, our multivariate analysis demonstrated that high SYNPO2 expression was substantially correlated with inferior disease-specific survival (hazard ratio = 1.968, P = .012) and local recurrence-free survival (hazard ratio = 3.386, P = .001). Overall, our findings reveal that SYNPO2 may aid in the development of potential prognostic biomarkers for NPC patients.
The effect of ferroptosis - related proteins and histone deacetylases1 on neoadjuvant chemotherapy in breast cancer
Authors: Sun Hong , Lin Ying , Liu Jia , Zheng Xiaohan , Wang Yiming , Cai Jiaqin , Wei Xiaoxia
Published: October 2023

Ferroptosis may improve the efficacy of tumor treatment, according to recent evidences. This study is to explore value of histone deacetylases 1 (HDAC1), ATP binding cassette subfamily B member 1 and ferroptosis-related proteins as potential predictive biomarkers. Eighty-two women who received neoadjuvant chemotherapy (NAC) confirmed breast cancer was included. Immunohistochemistry staining of HDAC1, ATP binding cassette subfamily B member 1 and ferroptosis-related proteins was performed in core needle biopsy and tumor resection tissue. Univariate and multivariate logistic regression were conducted to explore the potential biomarkers for breast cancer undergoing NAC. There was a weak positive correlation of HDAC1 level before and after NAC with imaging outcome (R = 0.390, P < .001). The expression of HDAC1 and glutathione peroxidase 4 before NAC was an independent predictor of imaging efficacy (OR = 7.633, CI 1.831–31.821, P < .001; OR = 0.700, CI 0.505–0.971, P < .05, respectively). HDAC1 and Glutathione peroxidase 4 may act as a new predictive biomarker for NAC in breast cancer. And personalized treatment can be provided based on them.
Evaluating disparities in code status designation among patients admitted with COVID-19 at a quaternary care center early in the pandemic
Authors: Olds Peter K. , Musinguzi Nicholas , Geisler Benjamin P. , Sarin Pankaj , Haberer Jessica E.
Published: October 2023

The COVID-19 pandemic has highlighted disparities in outcomes by social determinants to health. It is unclear how much end-of-life discussions and a patient’s decision about code status (“do not resuscitate,” do not resuscitate, or “comfort measures only,” [CMO] orders) might contribute to in hospital disparities in care, especially given know racial inequities in end-of-life care. Here, we looked at factors associated with code status orders at the end of hospitalization for patients with COVID-19. We conducted a retrospective chart review of all patients who presented to the Emergency Department of a large quaternary hospital between 8 March and 3 June 2020. We used logistic regression modeling to quantify the degree to which social determinants of health, including race, ethnicity, area deprivation index (ADI), English as a primary language, homelessness, and illicit substance use might impact the likelihood of a particular code status at the end-of a patient’s hospitalization, while controlling for disease severity. Among social determinants to health, only white race (odds ratio [OR] 2.0; P = .03) and higher ADI (OR 1.2; P = .03) were associated with having a do not resuscitate or a CMO order. Additionally, we found that patients with white race (OR 2.9; P = .02) were more likely to carry a CMO order. Patient race and ADI were associated with different code status orders at the end of hospitalization. Differences in code status might have contributed to disparities in COVID-19 outcomes early in the pandemic, though further investigations are warranted.
Expression of miR-223-3p in patients with hepatitis B virus liver fibrosis and its effect on hepatic stellate cells: An observational study
Authors: Hu Tingting , Zhang Wujing , Xu Chuanqin
Published: October 2023

To analyze miR-223-3p expression in patients with hepatitis B virus (HBV) live fibrosis and its effects on proliferation, activation, and apoptosis of human hepatic stellate cell line. One hundred patients with HBV-associated liver fibrosis were divided into S0 to 1, S2 to 3, and S4 groups according to Scheuer histological staging; healthy individuals during the same period were enrolled as healthy group. Relative expressions of miR-223-3p in healthy, S0 to 1, S2 to 3, and S4 groups were 0.56 ± 0.11, 1.08 ± 0.27, 2.16 ± 0.42, and 3.59 ± 1.06, respectively. Absorbance values of human hepatic stellate cell line cells at 24, 48, and 72 hours were higher in miR-223-3p-mimic group than in control group (CG) and NC-mimic group and were lower in miR-223-3p-inhibitor group than in CG and NC-inhibitor group (P < .05). mRNA miR-223-3p, α-smooth muscle actin, collagen 1A1, collagen 1A2, collagen 3A1, and transforming growth factor (TGF)-β1 levels were higher in miR-223-3p-mimic group than in CG and NC-mimic group and lower in miR-223-3p-inhibitor group than in CG and NC-inhibitor group (P < .05). Protein expressions of α-smooth muscle actin, transforming growth factor-β1, collagen I, collagen III, p-Smad3, p-Smad2, and B-cell lymphoma 2 were higher in miR-223-3p-mimic group than in CG and NC-mimic groups and lower in miR-223-3p-inhibitor group than in CG and NC-inhibitor group, whereas those of B-cell lymphoma 2-associated death promoter, B-cell lymphoma 2 associated X protein, cleaved caspase3, cleaved caspase9, poly ADP-ribose polymerase were lower in miR-223-3p-mimic group than in CG and NC-mimic group and higher in miR-223-3p-inhibitor group than in CG and NC-inhibitor group (P < .05). HBV liver fibrosis patients had elevated expression of miR-223-3p in plasma. Upregulation of miR-223-3p expression may be related to transforming growth factor-β1/Smad signaling pathway activation.
A case report of heterotopic gastric mucosa in the rectum treated by endoscopic submucosal dissection and a systematic review
Authors: Peng Dunhuang , Qiu Ting , Chen Shaohua , Hu Weitao , Fang Taiyong
Published: October 2023

Rationale:

Heterotopic gastric mucosa (HGM) can occur in all segments of the gastrointestinal tract, but rectal is very rare. In recent years, rectal HGM is more often treated by endoscopic resection (ER).

Patient concerns:

A 28-year-old female was admitted to the hospital with the chief complaint of “a rectal lesion found on physical examination”.

Diagnoses:

Heterotopic gastric mucosa (HGM).

Interventions:

An endoscopic submucosal dissection (ESD) was performed to completely dissect the lesion.

Outcomes:

The patient recovered well at 1 month of follow-up and did not suffer from further blood in the stool.

Lessons:

Rectal HGM has acid secretion function and HP can be colonized, causing a variety of symptoms such as abdominal pain, bloody stool, and anal pain and has the potential risk of malignant transformation; resection is the best treatment method, and ESD has its unique advantages and can be promoted in the clinic.
Effect of waiting time on patient satisfaction in outpatient: An empirical investigation
Authors: Zhang Hui , Ma Weimin , Zhou Shufen , Zhu Jingjing , Wang Li , Gong Kaixin
Published: October 2023

This study aimed to identify the effect of waiting time on patient satisfaction and the relationship between different types of waiting time. The questionnaire contained 2 parts. The first part included questions about expected waiting time (EWT), reasonable waiting time, tolerance waiting time, and basic personal information. The second part included perceived waiting time (PWT) and satisfaction evaluation. The actual waiting time (AWT) was recorded by the worker. Linear regression was used to analyze the influence of waiting time on satisfaction. Before data collection, this study was approved by the hospital’s health ethics committee. In total, 323 questionnaires were collected, of which 292 (90.4%) were valid. The EWT, tolerance waiting time, rational waiting time, and PWT had a significant effect on patient satisfaction (P = .006, P = .043, P = .009, P = .000), whereas AWT had no significant effect on satisfaction (P = .365). The difference between the EWT and AWT had a significant effect on satisfaction (P = .000), while the difference between the PWT and AWT had a significant effect on satisfaction (P = .000). Age, educational background, gender, appointment, and hospital visit experience had no significant effect on patient satisfaction (P = .105, P = .443, P = .260, P = .352, P = .461, respectively). Patient satisfaction with waiting time was not directly affected by AWT, but by subjective waiting times. Furthermore, objective waiting time affects patient satisfaction through the subjective waiting time. Therefore, hospital managers can improve service quality by focusing on adjusting a patient’s subjective waiting time while reducing the objective waiting time.
Pharmacological activities of esculin and esculetin: A review
Authors: Cai Ting , Cai Bin
Published: October 2023

Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini, which is a well-known herbal medicine with a 2000-year history. In vivo and in vitro studies have demonstrated that both have a variety of pharmacological activities, including antioxidant, anti-tumor, anti-inflammatory, antibacterial, antidiabetic, immunomodulatory, anti-atherosclerotic, and so on. Their underlying mechanisms of action and biological activities include scavenging free radicals, modulating the nuclear factor erythroid 2-related factor 2 pathway, regulating the cell cycle, inhibiting tumor cell proliferation and migration, promoting mitochondrial pathway apoptosis, inhibiting the NF-κB and MAPK signaling pathways, regulating CD4+ T cells differentiation and associated cytokine release, inhibiting vascular smooth muscle cells, etc. This review aims to provide comprehensive information on pharmacological studies of esculin and esculetin, which is of noteworthy importance in exploring the therapeutic potential of both coumarin compounds.
Gemtuzumab Ozogamicin Monotherapy Is a Well-tolerated Palliative Chemotherapy Option in Pediatric Multiply Relapsed Acute Myeloid Leukemia: A Multicenter Case Series and Review of the Literature
Authors: Blain Sarah , Payette Noémie , Bittencourt Henrique , Johnston Donna L.
Published: October 2023

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody that is Food and Drug Administration approved in upfront acute myeloid leukemia (AML) for patients over 1-month old, and for relapsed or refractory AML in patients over 2 years old. GO is now integrated in upfront pediatric AML treatment, and often in CD33+ relapse treatment combined with intensive conventional chemotherapy. Although GO was initially tested as a monotherapeutic agent in relapsed or refractory AML, there are few data in pediatric patients supporting this indication. In this review, we report 4 cases of multiply relapsed pediatric AML patients who were treated with GO monotherapy with palliative intent. Three of 4 patients obtained a complete response with GO reinduction, either as monotherapy or paired with conventional chemotherapy. Three patients remained in remission respectively for 5, 17, and 9 months with GO continuation monotherapy. The literature was reviewed regarding the use of GO in pediatric AML relapse settings.
Comparison of Confirmed Cytology Smears and Cell Blocks for Epidermal Growth Factor Receptor Mutation Testing in Non–Small Cell Lung Cancer
Authors: Liu Chia-Hsing , Chang Shu-Jyuan , Tsai Min-Jan , Yang Sheau-Fang
Published: October 2023

Introduction:

Various cytologic specimens have been used to diagnose epidermal growth factor receptor (EGFR) gene mutations in non–small cell lung cancer (NSCLC). However, insufficient samples and lengthy DNA extraction procedures have led to inconsistent diagnostic results. To reduce manipulation losses and improve DNA extraction quality, we provide an improved procedure for DNA extraction from smear samples containing rare tumor cells in NSCLC.

Patients and Methods:

The effectiveness of this new method for DNA extraction and diagnosis was validated in 8 patients with pleural effusion smears and formalin-fixed paraffin-embedded cell blocks, and another with 2 smears. Smear samples with <5% tumor cells were collected, and visible particles were selected for DNA extraction after centrifugation. Qiagen formalin-fixed paraffin-embedded DNA extraction kit (Qiagen) was used for DNA extraction and the procedure was modified. The EGFR mutation analysis in both types of material used the EGFR mutation analysis kit (Therascreen EGFR RGQ PCR) and real-time polymerase chain reaction (Rotor-Gene Q).

Results:

The DNA extraction amount of the smear was 2.6 to 258.8 ng/μL, and that of the cell block was 1.4 to 139.9 ng/μL. The DNA quantity and purity of DNA extracts isolated from both sample sources were sufficient for subsequent EGFR mutation detection, where mutation rates were similar and diagnostic results were consistent when smears or cell blocks were used.

Conclusion:

This improved method demonstrates that cytology smears can be used as a test material for the detection of EGFR mutations in patients with NSCLC with sparse cells.
Hereditary Ichthyosis With Gastrointestinal Manifestations: A Case Report
Authors: Tetarbe Shivangi , Jain Suhani , Shah Ira
Published: October 2023

Gut inflammation and defect in the gut mucosal barrier appear to have a correlation with skin diseases and vice versa. The coexistence of hereditary ichthyosis with active colitis has never been reported. We present a 17-year-old female with ichthyosis since birth, abdomen pain for 3 months, with acute colitis. After the initial diagnosis, the patient was started on antituberculous therapy (ATT), steroids, and mesalamine. She followed up with us for 1 year where there was resolution of symptoms. Steroids were stopped after 16 weeks, mesalamine was stopped after 20 weeks in view of low absolute neutrophil counts and ATT was stopped after 1 year. She was asymptomatic post 18 months of stopping ATT.
Amniotic Band Syndrome: Head-to-Toe Manifestations and Clinical Management Guidelines
Authors: Inglesby Dani C. , Janssen Pierce L. , Graziano Francis D. , Gopman Jared M. , Rutland John W. , Taub Peter J.
Published: October 2023

Learning Objectives:

After studying this article, the participant should be able to: 1. Understand and describe the basic principles underlying the intrinsic versus extrinsic proposed mechanisms for the development of amniotic band syndrome (ABS). 2. Discuss risk factors and conditions that are associated with the development of ABS. 3. Understand the various presentations and associated clinical implications of ABS by anatomic location. 4. Describe the basic tenets underlying various repair technique options for ABS of the extremities. 5. Discuss the common manifestations of ABS in the face and trunk. 6. Understand clinical implications of fetoscopic surgery as it relates to ABS treatment as a novel method for limb salvage in utero.

Amniotic band syndrome (ABS) refers to the development of constrictive bands of fibrotic tissue in utero. It can lead to a variety of clinical manifestations after delivery. There is much debate in the plastic surgery community regarding the exact pathophysiologic mechanism for the development of ABS, and the most appropriate management. This CME article aims to provide an overview of ABS manifestations throughout the body, and to expound on the most recent advances in anticipatory and definitive management of the condition.
Determination of Scalp Vascular Topography by Laser Doppler Flowmetry and Comparison of Vascular Damage by Different Blades in Hair Transplantation
Authors: Balik Ozan
Published: October 2023

Background:

Although necrosis is a rare complication in hair transplantation, it is extremely traumatic for both the patient and surgeon and also has potential medicolegal consequence. Studies have shown that ischemia in the recipient bed is related to tissue damage caused by the instruments used and the number of grafts per cm².

Objective:

We aimed to measure the effects of different instruments on circulation by dividing the recipient area of hair grafts of the same person into 2 sides as right and left.

Methods and Materials:

Sapphire percutaneous blade was used on the right side, and a handmade razor slit was used on the left side in 12 male patients with consent. Subsequently, vascularity was evaluated with laser Doppler flowmetry.

Results:

Scalp vascularity has so far only been evaluated with macroanatomic studies in the literature. First, the authors evaluated the effect of local anesthesia and adrenaline-containing swelling fluids on vascularity with a Laser Doppler Flowmeter. Afterward, the tissue damage caused by sapphire percutaneous blades and handmade blades (obtained from razor blades) were quantitatively analyzed and compared with each other.

Conclusions:

Our results showed that handmade razor blades caused significantly less tissue damage.
Introducing a new methodology to improve the predictive value of ancient woodland indicator species for landscape history
Authors: Baxter Alistair , Forbes-Laird Julian
Published: October 2023

Certain species of vascular plants have been proposed as indicators of very long established woodland. In the England and Wales, woodland present continuously since at least 1600AD is known as ‘ancient woodland’, with the plants concerned being referred to as ‘ancient woodland indicator species’. A number of authors have considered this topic from differing angles, and the concept has been validated, though with problems identified. The authors introduce a new method, WISDOM, for recording and analysing indicator assemblages, and test this tool with a comparative assessment of their distribution and occurrence in a known ancient woodland and a known secondary woodland. This paper reports the results of this assessment, discussing also the evidential weight that can be attached to different species of indicator plants. A literature review is included, with the authors concluding that their findings are consistent with several strands of previous research.
An Injectable Subcutaneous Colon-Specific Immune Niche For The Treatment Of Ulcerative Colitis
Authors: Au Kin Man , Wilson Justin E. , Ting Jenny P.-Y. , Wang Andrew Z.
Published: October 2023

As a chronic autoinflammatory condition, ulcerative colitis is often managed via systemic immunosuppressants. Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix, and nanofibers functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth-factor-beta 1, and the immunosuppressive small molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals’ lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive-T-cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon’s lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer, and eliminated immune-related colitis triggered by kinase inhibitors and immune-checkpoint blockade.
Study protocol for a multi-centre stepped-wedge cluster randomised trial to explore the usability and outcomes among young people living with HIV in Kiambu and Kirinyaga counties of Kenya, using an online health portal
Authors: Nturibi Eric , Mecha Jared , Kubo Elizabeth , Orwa Albert , Kaara Florence , Musau Faith , Wamuyu Christine , Kilonzi Justus , Gill Randeep , Roels Sanne
Published: October 2023

Introduction

While the incidence of HIV declines in most age groups globally, it continues to rise among adolescents and young adults who also experience a higher rate of HIV-related deaths. These tech-savvy individuals might benefit from an online patient portal aimed at increasing awareness, building skills, and promoting patient activation – the willingness and capacity to independently manage their health. However, the impact of such portals on young HIV patients in Kenya remains uncertain.

Methods and analysis

HIV patients aged 15-24 with smartphone access will participate in a 12-month stepped wedge cluster randomized trial. The main focus will be the portal’s effect on patient activation, with secondary outcomes being self-reported adherence, viral suppression, and social involvement. The study also aims to understand the portal’s development, implementation, functionality, usability, and cost. From 47 antiretroviral therapy (ART) sites with electronic medical recording systems, 16 clusters of 30 participants each will be formed. These clusters, over 12 months, will be randomized into 3 intervention sequences every 3 months. Baseline measurements, covering patient activation, adherence, viral load, and social engagement, will be recorded over two weeks, with subsequent checks at 3, 6, and 12 months. Data will be analyzed using generalised linear mixed models.

Ethics and dissemination

The protocol has received approval from the AMREF Health Africa Ethics & Scientific Review Committee (ESRC) and local governments. Findings will be shared through stakeholder forums, conferences, publications, and media.

Author Summary

What is the issue?

HIV infections among teenagers and young adults are increasing, particularly in Kenya. Given their technological inclination, an online portal might help them manage their health. The effectiveness of this approach remains uncertain.

What are our actions?

We are running a year-long study in Kenya with HIV-positive individuals aged 15 to 24 who have smartphones. The goal is to see if the portal aids their health management. We’re assessing health readiness, medication adherence, HIV control, and social connection. The study involves groups from 47 HIV treatment centers, with new groups engaging with the portal every three months.

What are our assessment methods?

We will use statistical methods to gauge the portal’s impact on health management.

Is the study approved?

Yes. It has endorsements from AMREF Health Africa and local governments. Results will be shared with the community, at conferences, in scientific journals, and in the media.
Anchoring of parasitic plasmids to inactive regions of eukaryotic chromosomes through nucleosome signal
Authors: Girard Fabien , Even Antoine , Thierry Agnès , Ruault Myriam , Meneu Léa , Adiba Sandrine , Taddei Angela , Koszul Romain , Cournac Axel
Published: October 2023

Natural plasmids are common in prokaryotes but few have been documented in eukaryotes. The natural 2µ plasmid present in budding yeastSaccharomyces cerevisiaeis one of the most well characterized. This highly stable genetic element coexists with its host for millions of years, efficiently segregating at each cell division through a mechanism that remains poorly understood. Using proximity ligation (Hi-C, Micro-C) to map the contacts between the 2µ and yeast chromosomes under dozens of different biological conditions, we found that the plasmid tether preferentially on regions with low transcriptional activity, often corresponding to long inactive genes. Common players in chromosome structure such as members of the structural maintenance of chromosome complexes (SMC) are not involved in these contacts which depend instead on a nucleosomal signal associated with a depletion of RNA Pol II. These contacts are stable throughout the cell cycle, and can be established within minutes. This strategy may involve other types of DNA molecules and species other thanS. cerevisiae, as suggested by the binding pattern of the natural plasmid along the silent regions of the chromosomes ofDictyostelium discoideum.
Human intestinal organoids with an autologous tissue-resident immune compartment
Authors: Recaldin Timothy , Gjeta Bruno , Steinacher Linda , Harter Marius F. , Adam Lukas , Nikolaev Mikhail , Krese Rok , Kilik Umut , Popovic Doris , Almató-Bellavista Marina , Kromer Kristina , Bscheider Michael , Cabon Lauriane , Camp J. Gray , Gjorevski Nikolche
Published: October 2023

The intimate relationship between the epithelium and the immune system is crucial for maintaining tissue homeostasis, with perturbations in epithelial-immune interactions linked to autoimmune disease and cancer. Whereas stem cell-derived organoids are powerful models of tissue-specific epithelial function, these structures lack tissue-resident immune cells that are essential for capturing organ-level processes. We describe human intestinal immuno-organoids (IIOs), formed through self-organization of epithelial organoids and autologous tissue-resident lymphocytes (TRMs), a portion of which integrate within the IIO epithelium and survey the barrier. IIO formation was driven by TRM migration and interaction with epithelial cells, as orchestrated by TRM-enriched transcriptomic programs governing cell motility and epithelial inspection. We combined IIOs and single-cell transcriptomics to investigate intestinal inflammation triggered by cancer-targeting biologics in patients, and found that the system recapitulates clinical outcomes and the underlying cellular mechanisms. Inflammation was associated with the emergence of an activated population of CD8+ T cells, which progressively acquired intraepithelial and cytotoxic features. The appearance of this effector population was preceded and likely mediated by a Th1-like CD4+ population, which initially displayed a cytokine-producing character and subsequently became cytotoxic itself. A system amenable to direct perturbation and interrogation, IIOs allowed us to identify the Rho pathway as a novel target for mitigating immunotherapy-associated intestinal inflammation. Given that they recapitulate both the phenotypic outcomes and the underlying inter-lineage immune interactions, IIOs can be used to broadly study tissue-resident immune responses in the context of tumorigenesis, infectious and autoimmune diseases.
Architecture and rearrangements of a sperm-specific Na+/H+exchanger
Authors: Pal Kamalendu , Chowdhury Sandipan
Published: October 2023

The sperm-specific sodium hydrogen exchanger, SLC9C1, underlies hyperpolarization and cyclic nucleotide stimulated proton fluxes across sperm membranes and regulates their hyperactivated motility. SLC9C1 is the first known instance of an ion transporter that uses a canonical voltage-sensing domain (VSD) and an evolutionarily conserved cyclic nucleotide binding domain (CNBD) to influence the dynamics of its ion-exchange domain (ED). The structural organization of this ‘tripartite transporter’ and the mechanisms whereby it integrates physical (membrane voltage) and chemical (cyclic nucleotide) cues are unknown. In this study, we use single particle cryo-electron microscopy to determine structures of a metazoan SLC9C1 in different conformational states. We find that the three structural domains are uniquely organized around a distinct ring-shaped scaffold that we call the ‘allosteric ring domain’ or ARD. The ARD undergoes coupled proton-dependent rearrangements with the ED and acts as a ‘signaling hub’ enabling allosteric communication between the key functional modules of sp9C1. We demonstrate that binding of cAMP causes large conformational changes in the cytoplasmic domains and disrupts key ARD-linked interfaces. We propose that these structural changes rescue the transmembrane domains from an auto-inhibited state and facilitate their functional dynamics. Our study provides a structural framework to understand and further probe electrochemical linkage in SLC9C1.
Study-Phase Reinstatement
Authors: Halpern David J. , Lega Bradley C. , Gross Robert E. , Wu Chengyuan , Sperling Michael R. , Aronson Joshua P. , Jobst Barbara C. , Kahana Michael J.
Published: October 2023

Can the brain improve the retrievability of an experience after it has occurred? Systems consolidation theory proposes that item-specific cortical reactivation during post-encoding rest periods facilitates the formation of stable memory representations, a prediction supported by neural evidence in humans and animals. Such reactivation may also occur on shorter time scales, offering a potential account of classic list memory phenomena but lacking in support from neural data. Leveraging the high-temporal specificity of intracranial electroencephalography (iEEG), we investigate spontaneous reactivation of previously experienced items during brief intervals between individual encoding events. Across two large-scale free recall experiments, we show that reactivation during these periods, measured by spectral iEEG similarity, predicts subsequent recall. In a third experiment, we show that the same methodology can identify post-encoding reactivation that correlates with subsequent memory, consistent with previous results. Thus, spontaneous study-phase reinstatement reliably predicts memory behavior, linking psychological accounts to neural mechanisms and providing evidence for rapid consolidation processes during encoding.
Targeting LC3/GABARAP for degrader development and autophagy modulation
Authors: Schwalm Martin P. , Dopfer Johannes , Kumar Adarsh , Greco Francesco A. , Bauer Nicolas , Löhr Frank , Heering Jan , Cano Sara , Lechner Severin , Hanke Thomas , Bekic Ivana , Morasch Viktoria , Fearon Daren , Marples Peter G. , Tomlinson Charles W. E. , Brunello Lorene , Saxena Krishna , Adams Nathan , von-Delft Frank , Müller Susanne , Stolz Alexandra , Proschak Ewgenij , Kuster Bernhard , Knapp Stefan , Rogov Vladimir V.
Published: October 2023

Recent successes in developing small-molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autophagosome tethering compounds (ATTECs) have received considerable attention from the drug development community. ATTECs are based on the target recruitment to LC3/GABARAP, a family of membrane-bound proteins that tether autophagy receptors to the autophagosome. In order to validate the existing ligands, we rigorously tested target engagement of reported ATTEC ligands and handles. Surprisingly, using various biophysical methods, most available ligands did not interact with their designated target LC3. Intrigued by the idea of developing ATTECs, we evaluated the druggability of LC3/GABARAP byin silicodocking and large scale crystallographic fragment screening. The data revealed that most fragments bound to the HP2, but not the HP1 pocket of the LC3-interacting region (LIR) docking site, suggesting favorable druggability of this binding pocket. Here, we present diverse comprehensively validated ligands for future ATTEC development.
Heparan-6-O-endosulfatase 2 promotes invasiveness of head and neck squamous carcinoma cell lines in co-cultures with cancer associated fibroblasts
Authors: Mukherjee Pritha , Zhou Xin , Benicky Julius , Panigrahi Aswini , Aljuhani Reem , Liu Jian , Ailles Laurie , Pomin Vitor H. , Wang Zhangjie , Goldman Radoslav
Published: October 2023

Local invasiveness of head and neck squamous cell carcinoma (HNSCC) is a complex phenomenon supported by interaction of the cancer cells with the TME. We and others have shown that CAFs are a component of the TME that can promote local invasion in HNSCC and other cancers. Here we report that the secretory enzyme Sulf-2 directly affects the CAF-supported invasion of HNSCC cell lines SCC35 and Cal33 into Matrigel. The Sulf-2 knockout (KO) cells differ from their wild type counterparts in their spheroid growths and formation, and the Sulf-2-KO leads to decreased invasion in a spheroid co-culture model with the CAF. Next, we investigated whether a fucosylated chondroitin sulfate isolated from the sea cucumberHolothuria Floridana(HfFucCS), affects activity of the Sulf-2 enzyme. Our results show that HfFucCS not only inhibits efficiently the Sulf-2 enzymatic activity but, like the Sulf-2 knockout, inhibits Matrigel invasion of the SCC35 and Cal33 cells co-cultured with the primary HNSCC CAF. These findings suggest that the heparan 6-O-endosulfatases regulate local invasion and could be therapeutically targeted with the inhibitory activity of a marine glycosaminoglycan.

Simple Summary

Local invasion of cancer cells is an early step in the cascade of metastasis that requires cooperation of multiple factors and cell types in the tumor microenvironment (TME). One important factor is the crosstalk of cancer cells with cancer associated fibroblasts (CAF). Here we explore the impact of a secretory enzyme heparan-6-O-endosulfatase 2 (Sulf-2) on the CAF-assisted invasion of head and neck squamous carcinoma cells into matrigel. We show that Sulf-2 knock out inhibits cancer cell invasion in a spheroid co-culture model and we identified a novel Sulf-2 inhibitor that, in the same model, limits cancer cell invasion.