bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of primary clear cell carcinoma of the liver based on Faster region-based convolutional neural network
Authors: Liu Bin , Li Jianfei , Yang Xue , Chen Feng , Zhang Yanyan , Li Hongjun
Published: October 2023

Background:

Distinguishing between primary clear cell carcinoma of the liver (PCCCL) and common hepatocellular carcinoma (CHCC) through traditional inspection methods before the operation is difficult. This study aimed to establish a Faster region-based convolutional neural network (RCNN) model for the accurate differential diagnosis of PCCCL and CHCC.

Methods:

In this study, we collected the data of 62 patients with PCCCL and 1079 patients with CHCC in Beijing YouAn Hospital from June 2012 to May 2020. A total of 109 patients with CHCC and 42 patients with PCCCL were randomly divided into the training validation set and the test set in a ratio of 4:1.The Faster RCNN was used for deep learning of patients' data in the training validation set, and established a convolutional neural network model to distinguish PCCCL and CHCC. The accuracy, average precision, and the recall of the model for diagnosing PCCCL and CHCC were used to evaluate the detection performance of the Faster RCNN algorithm.

Results:

A total of 4392 images of 121 patients (1032 images of 33 patients with PCCCL and 3360 images of 88 patients with CHCC) were uesd in test set for deep learning and establishing the model, and 1072 images of 30 patients (320 images of nine patients with PCCCL and 752 images of 21 patients with CHCC) were used to test the model. The accuracy of the model for accurately diagnosing PCCCL and CHCC was 0.962 (95% confidence interval [CI]: 0.931–0.992). The average precision of the model for diagnosing PCCCL was 0.908 (95% CI: 0.823–0.993) and that for diagnosing CHCC was 0.907 (95% CI: 0.823–0.993). The recall of the model for diagnosing PCCCL was 0.951 (95% CI: 0.916–0.985) and that for diagnosing CHCC was 0.960 (95% CI: 0.854–0.962). The time to make a diagnosis using the model took an average of 4 s for each patient.

Conclusion:

The Faster RCNN model can accurately distinguish PCCCL and CHCC. This model could be important for clinicians to make appropriate treatment plans for patients with PCCCL or CHCC.
Eosinophils in Traditionally Noneosinophil-Rich Dermatoses
Authors: Sanchez Isabella , Ibraheim Marina K. , Lee Bonnie A. , Kraus Christina N. , Elsensohn Ashley
Published: October 2023

The presence or absence of tissue eosinophilia has previously aided in the diagnosis of inflammatory skin conditions. However, recent studies have elucidated the presence of eosinophils in traditionally eosinophil-poor inflammatory skin diseases, such as dermatomyositis (DM), psoriasis, and lichen sclerosus (LS). This systematic review of the literature explores previous studies of tissue eosinophilia in skin biopsies of dermatoses that are believed to be classically poor in eosinophil. We identified 26 studies, the majority of which were retrospective reviews. The percent of specimens with increased eosinophils in psoriasis ranged from 18%–73%, pityriasis rubra pilaris (PRP) 22%–63%, LS 29%–53%, DM 15%–44%, morphea 8%–45%, hypertrophic lichen planus (LP) 0%–21%, and oral LP 0%–4%. These reports of tissue eosinophilia in reputed eosinophil-poor dermatologic conditions present a diagnostic pitfall and suggest that tissue eosinophilia itself should not be used to rule out a diagnosis of one of these conditions.
The Differences in the Practice of Cosmetic Dermatologic Procedures Between Physicians and Nonphysicians
Authors: Aleisa Abdullah , Lu Jasmine Thai , Al Saud Aljohara , Veldhuizen Inge J. , Rossi Anthony M. , Lee Kachiu C.
Published: October 2023

BACKGROUND

With a rise in demand for cosmetic dermatologic procedures comes an increase in nonphysician providers performing such procedures. However, little is known about the practice of cosmetic procedures performed by nonphysicians.

OBJECTIVE

To assess the differences in the practice of cosmetic procedures provided by physicians and nonphysicians.

MATERIALS AND METHODS

A cross-sectional analysis was performed using participant (n = 4,062) responses to an 18-point, web-based survey about previous cosmetic procedures.

RESULTS

In total, 1,328 participants reported having previous cosmetic procedures done by a physician (n = 828), a nonphysician (n = 413), or an unknown provider (n = 87). Respondents of all age ranges and male respondents (p < .001) tended to choose physicians over nonphysician providers when choosing a practice. Moderate adverse events were more frequently seen when nonphysician providers completed cosmetic procedures (p < .001). Despite a higher frequency (73.3% vs 51.8%) of more moderate complications seen in procedures done by nonphysician providers, over 70% of respondents believe that nonphysician providers are qualified enough to continue performing cosmetic procedures.

CONCLUSION

People should be encouraged to make an informed decision when choosing a provider because cosmetic procedures are still considered medical procedures.
Reopening the capsular bag by removing the capsular proliferative membrane to enable secondary in-the-bag intraocular lens implantation in pediatric aphakic eyes
Authors: Zhou Yue , Zhang Yu , Chen Hui , Bai Bingyu , Wang Qiwei , Lin Zhuoling , Li Jing , Zhang Xiulan , Chen Wan , Chen Weirong
Published: October 2023

Purpose:

To present a surgical technique for reopening the capsular bag in pediatric aphakia.

Setting:

Zhongshan Ophthalmic Center, Guangzhou, China.

Design:

Case series study.

Methods:

Consecutive pediatric patients with bilateral aphakia requiring secondary intraocular lens (IOL) implantation between July 2021 and June 2022 were included. The diameter of the capsular proliferative membranous ring (PMR) and position of IOL implantation were documented. Various parameters of capsular bag opening during primary cataract removal and secondary surgery were also analyzed.

Results:

48 eyes were included with a mean follow-up of 8.1 ± 4.4 months. Using the surgical technique developed in this study, the capsular bag was successfully reopened with in-the-bag (ITB) implantation in 43 eyes (89.6%). ITB implantation was accomplished in all eyes with an outer diameter of PMR ≤5.5 mm and in 3 of 8 eyes (37.5%) with an outer diameter of PMR >5.5 mm. A positive correlation was observed between the primary and secondary anterior capsular opening diameters (ACODs) (r = 0.422, P = .007) and the primary and secondary posterior capsular opening diameters (PCODs) (r = 0.619, P < .001). The inner diameter of PMR was found to be positively correlated with secondary PCOD (r = 0.728, P < .001) and the outer diameter with secondary ACOD (r = 0.669, P < .001).

Conclusions:

This was a safe and effective surgical technique for pediatric secondary IOL implantation with maximum preservation of the peripheral capsule. Aphakic eyes with an outer diameter of PMR ≤5.5 mm are preferred for secondary ITB implantation.
Effect of tibolone vs hormone replacement therapy on climacteric symptoms and psychological distress
Authors: Hsiao Sheng-Mou , Liao Shih-Cheng
Published: October 2023

Background:

The objective was to elucidate the effect of tibolone vs hormone replacement therapy (HRT) on climacteric symptoms and psychological distress.

Methods:

All consecutive women with climacteric symptoms were allocated to receive tibolone (2.5 mg) or estradiol valerate (1 mg) plus medroxyprogesterone acetate (2.5 mg).

Results:

The improvement in “feeling dizzy or faint” after tibolone treatment was more prominent than that after HRT (−0.7 ± 0.8 vs −0.0 ± 0.9, p = 0.004). In addition, other climacteric symptoms, including anxiety, depression, somatic symptoms, and vasomotor symptoms, and sexual function improved after tibolone and HRT, but there were no between-group differences. Psychological distress assessment demonstrated that somatic complaints, obsessive-compulsive symptoms, depressive symptoms, hostility, additional symptoms, and the General Symptom Index improved after tibolone treatment and HRT, but there were no between-group differences. Personality traits assessment revealed that neuroticism improved after tibolone treatment.

Conclusion:

Tibolone seems more beneficial than HRT in treating symptoms of dizziness and faintness. Both tibolone and HRT could improve psychological distress.
Diagnostic Yield, Radiation Exposure, and the Role of Clinical Decision Rules to Limit Computed Tomographic Pulmonary Angiography–Associated Complications
Authors: Perelas Apostolos , Kirincich Jason , Yadav Ruchi , Ennala Sravanti , Wang Xiaofeng , Sadana Divyajot , Duggal Abhijit , Krishnan Sudhir
Published: October 2023

Objectives

Computed tomographic pulmonary angiography (CT-PA) is associated with significant cost, contrast, and radiation exposure. Clinical decision rules (CDRs) reduce the need for diagnostic imaging; however, their utility in the medical intensive care unit (MICU) remains unknown. We explored the diagnostic yield and complications associated with CT-PA (radiation exposure and contrast-induced acute kidney injury [AKI]) while investigating the efficacy of CDRs to reduce unnecessary testing.

Methods

All CT-PAs performed in an academic MICU for 4 years were retrospectively reviewed. The Wells and revised Geneva scores (CDRs) and radiation dose per CT-PA were calculated, and the incidence of post–CT-PA AKI was recorded.

Results

A total of 439 studies were analyzed; the diagnostic yield was 11% (48 PEs). Positive CT-PAs were associated with a higher Wells score (5.8 versus 3.2, P < 0.001), but similar revised Geneva scores (6.4 versus 6.0, P = 0.32). A Wells score of ≥4 had a positive likelihood ratio of 2.1 with a negative predictive value of 98.2. More than half (88.9%) of patients with a Wells score of ≤4 developed an AKI, with 55.6% of those having recovery of renal function.

Conclusions

There is overutilization of CT-PA in the MICU. The Wells score retains its negative predictive value in critically ill adult patients and may aid to limit radiation exposure and contrast-induced AKI in MICU.
Fracture Risk and Association With TDF Use Among People With HIV in Large Integrated Health Systems
Authors: Hechter Rulin C. , Zhou Hui , Leyden Wendy A. , Yuan Qing , Pak Katherine J. , Lam Jennifer O. , Alexeeff Stacey , Lea Alexandra , Hu Haihong , Marcus Julia L. , Rivera Adovich S. , Adams Annette L. , Horberg Michael A. , Towner William J. , Lo Joan C. , Silverberg Michael J.
Published: October 2023

Background:

Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear.

Setting:

Retrospective analyses of electronic health record data from 3 US integrated health care systems.

Methods:

Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART.

Results:

Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40–49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58).

Conclusions:

Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening.
Brief Report: The Virome of Bladder Tumors Arising in People Living With HIV
Authors: Starrett Gabriel J. , Foster Haidn , Sigel Keith , Liu Yuxin , Engels Eric A.
Published: October 2023

Background:

People living with HIV (PLWH) have elevated risk for developing virus-related cancers. Bladder cancer risk is not increased in PLWH but is elevated among immunosuppressed solid organ transplant recipients (SOTRs). BK polyomavirus and, to a lesser extent, other viruses have been detected in bladder cancers from SOTRs.

Objective:

To characterize the virome of bladder tumors in PLWH.

Design:

Retrospective case series.

Methods:

We sequenced DNA and RNA from archived formalin-fixed bladder tumors from PLWH. Nonhuman reads were assembled and matched to a database of known viruses.

Results:

Fifteen bladder tumors from PLWH (13 carcinomas, 2 benign tumors) were evaluated. Fourteen tumors were in men, and the median age at diagnosis was 59 years (median CD4 count 460 cells/mm3). All but 1 tumor yielded both sufficient DNA and RNA. One bladder cancer, arising in a 52-year-old man with a CD4 count of 271 cells/mm3, manifested diverse Alphatorquevirus DNA and RNA sequences. A second cancer arising in a 58-year-old male former smoker (CD4 count of 227 cells/mm3) also showed Alphatorquevirus and Gammatorquevirus DNA sequences. Neither tumor exhibited viral integration.

Conclusions:

Alphatorqueviruses and Gammatorqueviruses are anelloviruses, which have also been detected in bladder cancers from SOTRs, but anelloviruses are common infections, and detection may simply reflect increased abundance in the setting of immunosuppression. The lack of detection of BK polyomavirus among bladder tumors from PLWH parallels the lower level of bladder cancer risk seen in PLWH compared with SOTRs, indirectly supporting a role for BK polyomavirus in causing the excess risk in SOTRs.
Which Intervention Synergies Maximize AGYW's HIV Outcomes? A Classification and Regression Tree Analysis of Layered HIV Prevention Programming
Authors: Mathur Sanyukta , Mahapatra Bidhubhusan , Mishra Raman , Heck Craig J. , Mbizvo Michael
Published: October 2023

Introduction:

Intersecting behavioral, social, and structural factors increase adolescent girls' (AG) and young women's (YW) HIV vulnerability. Yet, understanding of optimal intervention synergies remains limited. We identified intervention combinations that statistically maximized reductions in AGYW's HIV-related risk.

Methods:

Using data collected in 2018 with Zambian AG (n = 487, aged 15–19 years) and YW (n = 505, aged 20–25 years) after 12–14 months exposure to Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (multisectoral HIV program), we used classification and regression trees to explore relationships between interventions (safe space/social asset building [SAB] and provision of/linkage to youth-friendly health services [YFHS], education social protection [Educ], economic social protection [Econ]) and HIV-related outcomes (HIV testing, consistent condom use, transactional sex, and sexual violence experience from partners and nonpartners).

Results:

Overall, 59.9% completed SAB and 81.5%, 35.4%, and 29.6% received YHFS, Educ, and Econ, respectively. For AG, HIV testing improved (from 73% to 83%) with exposure to all interventions, condom use improved with Econ (from 33% to 46%), transactional sex reduced with SAB + Educ, and sexual violence from partners and nonpartners reduced with Educ and SAB, respectively. For YW, HIV testing increased with Educ (from 77% to 91%), condom use increased with SAB + YFHS (from 36% to 52%), transactional sex reduced with combinations of all interventions, and sexual violence from partners reduced with YFHS and from nonpartners with SAB + Econ.

Conclusions:

Tailored interventions might be more effective than uniform combination intervention packages in reducing AGYW's HIV risk. AG benefitted most from SAB and/or Educ while YFHS, Educ, and/or SAB reduced YW's HIV-related risk. Educational and asset-building interventions could have the greatest impact on AGYW's HIV risk.
FDG PET/CT in a Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor
Authors: Guo Jia , Liao Zhongjian , Chen Qing , Dong Aisheng , Huang Mouqing
Published: October 2023

Thoracic SMARCA4-deficient undifferentiated tumor is a rare, newly recognized poorly differentiated tumor with poor prognosis. FDG PET/CT findings of thoracic SMARCA4-deficient undifferentiated tumor are rarely reported. We describe FDG PET/CT findings in a case of thoracic SMARCA4-deficient undifferentiated tumor. The tumor presented as a pleural mass, destroyed the adjacent ribs, and showed intense FDG uptake with SUVmax of 12.7. This case indicates that thoracic SMARCA4-deficient undifferentiated tumor should be included in the differential diagnosis of FDG-avid pleural lesions.
Extramedullary Hematopoiesis in Treated Diffuse Large B-Cell Lymphoma of Bone
Authors: Chaouki Amine , Roelants Véronique , Gheysens Olivier , Bailly Sarah , Krug Bruno
Published: October 2023

A 65-year-old man with a history of diffuse large B-cell bone lymphoma of the right radius underwent an interim FDG PET/CT after 2 cycles of chemotherapy. Besides a complete metabolic response on the primary site, images revealed a hypermetabolic nodule in the posterior mediastinum, not present on the initial images. The metabolic activity of the nodule was similar to that of the reactive bone marrow and disappeared, concomitantly to the normalization of the medullar signal on the posttreatment images. The similarity and synchronous metabolic activity evolution in the nodule and bone marrow indicate extramedullary hematopoiesis.
Asymptomatic Penetrating Atherosclerotic Ulcer Findings on 18F-FDG PET/CT
Authors: Murad Vanessa , Ortega Claudia , Hanneman Kate , Chung Jennifer , Metser Ur
Published: October 2023

We present a case of an 84-year-old man with a history of smoking, hypertension, and coronary artery disease with an incidental spiculated left apical pulmonary nodule, suspicious for a stage I non–small cell lung cancer. 18F-FDG PET/CT performed for staging, which confirmed a small metabolically active pulmonary nodule. As an incidental finding, there was focal FDG uptake in the proximal descending aorta corresponding to a partially thrombosed outpouching of the aortic wall, in keeping with a penetrating atherosclerotic ulcer.
PSMA Radioligand Therapy in Prostate Cancer
Authors: Almeida Ludmila Santiago , Etchebehere Elba Cristina Sá de Camargo , García Megías Irene , Calapaquí Terán Adriana K. , Hadaschik Boris , Colletti Patrick M. , Herrmann Ken , Giammarile Francesco , Delgado Bolton Roberto C.
Published: October 2023

Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific membrane antigen agents has been proven beneficial in certain clinical indications. In this review, we describe management of prostate cancer patients according to current guidelines, especially focusing on the available clinical evidence for prostate-specific membrane antigen radioligand therapy.
Synchronous Endometrial Cancer Detected on 68Ga-DOTATATE PET/CT
Authors: Mohammadinejad Payam , Kim Alex , Koshevarova Victoria , Murphy Micah , Shagun FNU , Bhargava Peeyush
Published: October 2023

A 50-year-old woman with history of metastatic neuroendocrine tumor underwent a follow-up PET/CT with 68Ga-DOTATATE. An enlarged uterus with diffuse increased uptake warranted further investigation with an MRI that showed mass-like thickening of the endometrium, T2 hyperintensity, lobulated contour, and invasion of more than 50% of the myometrium. Biopsy revealed endometrial carcinoma with mucinous features. Mild to moderate uptake of the 68Ga-DOTATATE by the uterus can be a normal physiological finding; however, it should prompt further investigation, particularly in a postmenopausal woman with concerning imaging or clinical findings.
Objective Changes in Pelvic Floor Muscle Strength and Length in Women With High-Tone Pelvic Floor Dysfunction After Pelvic Floor Physical Therapy (RELAX Trial)
Authors: Volpe Lena J. , Zugelder Morgan , Kotarinos Rhonda , Kotarinos Elizabeth , Kenton Kimberly , Geynisman-Tan Julia
Published: October 2023

Importance

Although pelvic floor physical therapy (PFPT) is effective in treating high-tone pelvic floor dysfunction (HTPFD), data on the mechanism of improvement are limited.

Objectives

This study aimed to compare squeeze intravaginal closure force after 6 weeks of PFPT in women affected by HTPFD and, secondarily, to describe changes in levator dimensions and short-term effects of PFPT on bladder, bowel, and pain symptoms.

Methods

We conducted a prospective cohort study of patients undergoing 6 sessions of PFPT for the diagnosis of HTPFD. At baseline, we measured intravaginal closure force using an instrumented speculum, levator hiatal dimension using a 3-dimensional endovaginal ultrasonography, and symptom severity using 3 validated questionnaires. Intravaginal closure force and symptoms were reevaluated after the second, fourth, and sixth PFPT sessions, and levator hiatus was reevaluated at the sixth session.

Results

Twenty-six women were enrolled and 22 completed 6 sessions and are included in the analysis. Contrary to our hypothesis, mean ± SD vaginal closure force (N) did not demonstrate a significant change (3.27 ± 2.34 vs 3.67 ± 2.02 N, P = 0.18). However, mean levator hiatal area (cm2) increased between visit 1 (13.71 ± 1.77 cm2) and visit 6 (14.43 ± 2.17 cm2, P = 0.05), as did the transverse diameter (3.83 ± 0.03 vs 3.95 ± 0.03 cm, P = 0.04). Survey responses demonstrated significant improvements across all measures of genitourinary symptoms, pain, lower gastrointestinal symptoms and quality-of-life measures after 6 sessions of PFPT.

Conclusion

Although the levator hiatal area increased after 6 sessions of PFPT (suggesting muscle lengthening), we were unable to demonstrate that this changed the force generated by pelvic floor muscles as measured by a speculum.
Perioperative Outcomes for Same- Versus Next-Day Discharge After Benign Vaginal Hysterectomy
Authors: Burger Kristina A. , Robison Elizabeth H. , Nekkanti Silpa , Hundley Andrew F. , Hudson Catherine O.
Published: October 2023

Importance

While same-day discharge (SDD) after laparoscopic hysterectomy is well supported, studies for vaginal hysterectomy (VH) are lacking.

Objective

The aim of the study was to compare 30-day complications for SDD versus next-day discharge (NDD) after benign VH.

Study Design

This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2019. Vaginal hysterectomy with or without urogynecology procedures was identified by Current Procedural Terminology codes. The primary outcome was 30-day composite complications of SDD versus NDD after VH. Secondary outcomes compared reoperations rates, time to and reasons for reoperation, and complications between the groups. Composite complications included death, major infection or wound complication, thromboembolism, transfusion, cardiopulmonary complication, renal insufficiency/failure, stroke, or reoperation. Unadjusted and adjusted odds ratios were determined using univariate and multivariate analysis.

Results

Of 24,277 people included, 4,073 (16.8%) were SDD, which were more likely to be younger (P < 0.001), less likely to have hypertension (23.4 vs 18.3%, P < 0.0001) or diabetes (4.5 vs 3.3%, P = 0.001), and had shorter surgical procedures (100.7 ± 47.5 vs 111.2 ±57.5 minutes, P < 0.0001). There was no difference in composite complications after SDD versus NDD and this remained true in multivariate analysis (2.0 vs 2.3%, P = 0.30, SDD; adjusted odds ratio, 0.9; 95% confidence interval, 0.7–1.1). There was no difference in reoperation rates (0.9 vs 0.9%, P = 0.94) or reasons for reoperation. Time to first complication was shorter for SDD versus NDD (11 vs 13 days, P = 0.47).

Conclusion

In our cohort of low-risk patients, SDD after VH with or without urogynecology procedures did not have an increased odds of 30-day composite complications.
The Injured Monocyte: The Link to Chronic Critical Illness and Mortality Following Injury
Authors: Cuschieri Joseph , Kornblith Lucy , Pati Shibani , Piliponsky Adrian
Published: October 2023

Background

This study aimed to understand the altered innate immune response in severely injured patients leading to chronic critical illness (CCI). Specifically, it focused on characterizing the monocyte populations and their correlation with CCI development and long-term complications.

Methods

Over a 3-year period, we monitored patients with severe injuries for up to 1-year post-injury. CCI was defined as an ICU stay exceeding 14 days with persistent organ failure. Blood samples were collected on days 1 and 5 for monocyte phenotypic expression analysis using cytometry by time flight. The monocyte subpopulations studied were classical (CL), intermediate (INT), and non-classical (NC), along with cell surface receptor expression and activation.

Results

Out of 80 enrolled patients, 26 (32.5%) developed CCI. Patients with CCI had more severe injuries (injury severity score 32.4 + 5.2 vs. 29.6 + 4.1, p = 0.01) and received a higher number of red blood cells (8.9 + 4.1 vs. 4.7 + 3.8 units, p < 0.01) compared to those without CCI. In patients with CCI, the NC monocytes were significantly reduced by over 2-fold early, and significantly increased later, compared to those without CCI. Moreover, significant changes in intracellular cytokine expression and cell receptors were observed within each monocyte subpopulation in patients with CCI, indicating an increased pro-inflammatory phenotype but decreased phagocytic capacity and antigen presentation. The development of CCI and the presence of this unique monocyte phenotype were associated with a significantly increased risk of infection, discharge to a long-term care facility, and 1-year mortality of 27%.

Conclusions

Development of CCI following severe injury is associated with significant long-term morbidity and unacceptably high mortality. The altered NC phenotype with reduced phagocytic capacity and antigen presentation in patients developing CCI after severe injury is appears partially responsible. Early identification of this unique phenotype may help predict and treat patients at risk for CCI, leading to improved outcomes.

Level of Evidence

Level III, Prognostic/Epidemiological
A heterogenous population of extracellular vesicles mobilize to the alveoli postinjury
Authors: Costantini Todd W. , Park Dong Jun , Johnston William , Nakatsutsumi Keita , Kezios Jenny , Weaver Jessica L. , Coimbra Raul , Eliceiri Brian P.
Published: October 2023

BACKGROUND

Acute lung injury and subsequent resolution following severe injury are coordinated by a complex lung microenvironment that includes extracellular vesicles (EVs). We hypothesized that there is a heterogenous population of EVs recruited to the alveoli postinjury and that we could identify specific immune-relevant mediators expressed on bronchoalveolar lavage (BAL) EVs as candidate biomarkers of injury and injury resolution.

METHODS

Mice underwent 30% TBSA burn injury and BAL fluid was collected 4 hours postinjury and compared with sham. Extracellular vesicles were purified and single vesicle flow cytometry (vFC) was performed using fluorescent antibodies to quantify the expression of specific cell surface markers on individual EVs. Next, we evaluated human BAL specimens from injured patients to establish translational relevance of the mouse vFC analysis. Human BAL was collected from intubated patients following trauma or burn injury, EVs were purified, then subjected to vFC analysis.

RESULTS

A diverse population of EVs were mobilized to the alveoli after burn injury in mice. Quantitative BAL vFC identified significant increases in macrophage-derived CD44+ EVs (preinjury, 10.8% vs. postinjury, 13%; p < 0.05) and decreases in IL-6 receptor alpha (CD126) EVs (preinjury, 19.3% vs. postinjury, 9.3%, p < 0.05). Bronchoalveolar lavage from injured patients also contained a heterogeneous population of EVs derived from myeloid cells, endothelium, and epithelium sources, with CD44+ EVs being highly detected.

CONCLUSION

Injury causes mobilization of a heterogeneous population of EVs to the alveoli in both animal models and injured patients. Defining EV release after injury will be critical in identifying diagnostic and therapeutic targets to limit postinjury acute lung injury.
Idiopathic Ileal Ulceration After Intestinal Transplantation
Authors: Hussan Elsadig , Kroemer Alexander , Elsabbagh Ahmed M. , Khan Khalid M. , Yazigi Nada A. , Ekong Udeme D. , Subramanian Sukanya , Ghobrial Shahira S. , Guerra Juan-Francisco , Fishbein Thomas M. , Matsumoto Cal S. , Kaufman Stuart S.
Published: October 2023

Background.

Idiopathic ileal ulceration after intestinal transplantation (ITx) has been discussed infrequently and has an uncertain natural history and relation to graft rejection. Herein, we review our experience with this pathology.

Methods.

We retrospectively reviewed 225 ITx in 217 patients with minimum 1 y graft survival. Routine graft endoscopy was conducted up to twice weekly within the first 90 d after ITx, gradually decreasing to once yearly. Risks for ulceration over time were evaluated using Cox regression.

Results.

Of 93 (41%) patients with ulcers, 50 were found within 90 d after ITx mostly via ileoscopy; delayed healing after biopsy appeared causal in the majority. Of the remaining 43 patients with ulcers found >90 d after ITx, 36 were after ileostomy closure. Multivariable modeling demonstrated within 90-d ulcer associations with increasing patient age (hazard ratio [HR], 1.027; P < 0.001) and loop ileostomy (versus Santulli ileostomy; HR, 0.271; P < 0.001). For ulcers appearing after ileostomy closure, their sole association was with absence of graft colon (HR, 7.232; P < 0.001). For ulcers requiring extended anti-microbial and anti-inflammatory therapy, associations included de novo donor-specific antibodies (HR, 3.222; P < 0.007) and nucleotide oligomerization domain mutations (HR, 2.772; P < 0.016). Whole-cohort post-ITx ulceration was not associated with either graft rejection (P = 0.161) or graft failure (P = 0.410).

Conclusions.

Idiopathic ulceration after ITx is relatively common but has little independent influence on outcome; risks include ileostomy construction, colon-free ITx, immunologic mutation, and donor sensitization.
The role of polycystic ovary syndrome in preclinical left ventricular diastolic dysfunction: an echocardiographic approach: a systematic review and meta-analysis
Authors: Mirzohreh Seyedeh-Tarlan , Panahi Padideh , Zafardoust Hooman , Zavvar Morteza , Fathi Nima , Dehghan Mahshid , Sarbakhsh Parvin
Published: October 2023

Background

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of childbearing age, causing hormonal imbalances, reproductive issues, and metabolic disturbances. Women with PCOS have an increased risk of cardiovascular disease due to insulin resistance, obesity, and hyperandrogenism. Detecting impaired left ventricular (LV) function is important in managing this condition. Echocardiography, a non-invasive imaging technique, can effectively detect LV dysfunction.

Aim

The goal of this systematic review was to assess whether there are any variations in echocardiographic measures between women with PCOS and those without the condition in order to determine the potential impact of PCOS on LV function.

Methods

This review followed the PRISMA reporting guidelines. A thorough search of databases including PubMed, Scopus, Web of Science, and Cochrane was conducted. The quality of the selected studies was assessed using the Joanna Briggs Institute appraisal instruments. After applying strict eligibility criteria, data were extracted and organized in Microsoft Excel sheets. Review Manager (RevMan) software was used for the analysis.

Results

Analysis of 29 studies revealed significant differences in echocardiographic measures related to diastolic function between women with PCOS and healthy controls. However, there were no significant differences in measures of systolic function.

Conclusion

These findings indicate that PCOS may be linked to impaired LV function, thereby increasing the risk of cardiovascular disease. Further research is necessary to better understand this association and its clinical implications. Early detection and management of PCOS could potentially help prevent cardiovascular complications in affected women.
Chakrabartyella piscis gen. nov., sp. nov., a member of the family Lachnospiraceae, isolated from the hindgut of the marine herbivorous fish Kyphosus sydneyanus
Authors: Pardesi Bikiran , Roberton Anthony M. , Wollmuth Emily M. , Angert Esther R. , Rosendale Douglas I. , White William Lindsey , Clements Kendall D.
Published: October 2023

A Gram-stain-negative, non˗spore-forming, rod˗shaped, obligately anaerobic bacterium, designated strain BP5GT, was isolated from the hindgut of a silver drummer (Kyphosus sydneyanus) fish collected from the Hauraki Gulf, New Zealand. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the isolate belonged to the family

Lachnospiraceae

in the phylum

Bacillota

and was most closely related to

Anaerotignum propionicum

with 94.06 % sequence identity. Isolate BP5GT grew on agar medium containing mannitol and fish gut fluid as carbon sources. Clear colonies of approximately 1 mm diameter of the isolate grew within a week at 20–28 °C (optimum, 28 °C) and pH 7.6–8.5 (optimum, pH 8.5). Strain BP5GT was very sensitive to NaCl and the optimal concentration for growth was 0.045 % (w/v). Acetate and propionate were the major fermentation products. The major cellular fatty acids were C12 : 0, C14 : 0, C15 : 0 and C16 : 0. The genome sequence of the isolate was determined. Its G+C content was 38.41 mol% and the 71.41 % average nucleotide identity of the BP5GT genome to its closest neighbour with a sequenced genome (

A. propionicum

DSM 1682T) indicated low genomic relatedness. Based on the phenotypic and taxonomic characteristics observed in this study, a novel genus and species named Chakrabartyella piscis gen. nov., sp. nov. is proposed for isolate BP5GT (=ICMP 24687T=JCM 35769T).
Systems genetics identifies the association between Enc1 and cognitive function in the hippocampus
Authors: He Hongjie , Tao Ran , Han Zhe , Yin Quanting , Pan Shuijing , Lu Lu , Bajpai Akhilesh Kumar , Mi Jia , Qi Donglai , Li He , Xu Fuyi
Published: October 2023

Ectodermal-Neural Cortex 1 (ENC1) is expressed in multiple regions of the brain, including the hippocampus. However, knowledge about its function has been well explored only in the context of peroxidative stress and cancer. In this study, we investigated the association of hippocampal Enc1 with cognitive function in BXD mice. We performed Pearson correlation, phenotype-wide association analysis (PheWAS), expression-Based PheWAS, pathway enrichment, and protein interaction networks on Enc1 and BXD phenotypes/transcriptome of the hippocampus, and the results indicated that Enc1 is inextricably linked to cognitive performance. In addition, we found that most of theEnc1co-expressed genes were highly expressed in GABAergic neuronal cells. Expression quantitative trait loci analysis indicated that Enc1 wascis-regulated in the hippocampus of mice as well as human. Genome-wide association analysis revealed ENC1 to be significantly associated with cognitive-related traits, including age-related cognitive changes etc. In conclusion, our findings demonstrated thatEnc1is involved in cognitive functions mainly in hippocampal GABAergic neuronal cells through neurogenesis, synaptic signaling, and CGMP-PKG signaling pathways, and interacts with the neurological function-related genes.
In-vitro digestion models to examine the effects of Plant-Based Meat substitutes on Gut Microbial Metabolites
Authors: Izquierdo-Sandoval David , Duan Xiang , Fryganas Christos , Portolés Tania , Sancho Juan Vicente , Rubert Josep
Published: October 2023

The increasing popularity of plant-based meat alternatives (PBMAs) has triggered a contentious debate about their impact on gut health in comparison to traditional animal-based meats. This study investigates the digestibility and bioavailability of a beef patty, a commercial PBMA, and a homemade pea protein-based ’patty’ by examining their influence on gut microbial metabolism. Fecal samples from five different donors were utilized to replicate colonic fermentation in vitro, with samples collected at various time points (0, 6, 12, 24, 32, and 48 hours). A rapid biochemical profiling, comparing red meat and meat analogs in terms of traditional biomarkers of gut health (ammonia, phenols, indoles, pH, and short-chain fatty acids), was conducted. Additionally, an untargeted metabolomics workflow specially designed for time-series studies, utilizing ultra-high performance liquid chromatography hyphenated to a quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS), was implemented to assess differences in terms of protein-related gut microbial metabolites (GMMs). The findings of this approach revealed notable differences in the production of intestinal inflammation markers, metabolites related to the carnitine pathways, and GMMs with signaling functions in the intestinal tract during the fermentation of animal- and plant-based burgers.
Mycobacterial DnaQ is an Alternative Proofreader Ensuring DNA Replication Fidelity
Authors: Deng Ming-Zhi , Liu Qingyun , Cui Shu-Jun , Fu Han , Gan Mingyu , Xu Yuan-Yuan , Cai Xia , Sha Wei , Zhao Guo-Ping , Fortune Sarah M. , Lyu Liang-Dong
Published: October 2023

Remove of mis-incorporated nucleotides ensures replicative fidelity. Although the ε-exonuclease DnaQ is a well-established proofreader in the model organismEscherichia coli, proofreading in mycobacteria relies on the polymerase and histidinol phosphatase (PHP) domain of replicative polymerase despite the presence of an alternative DnaQ homolog. Here, we show that depletion of DnaQ inMycolicibacterium smegmatisresults in increased mutation rate, leading to AT-biased mutagenesis and elevated insertions/deletions in homopolymer tract. We demonstrated that mycobacterial DnaQ binds to the β-clamp and functions synergistically with the PHP domain to correct replication errors. Further, we found that the mycobacterial DnaQ sustains replicative fidelity upon chromosome topological stress. Intriguingly, we showed that a naturally evolved DnaQ variant prevalent in clinicalMycobacterium tuberculosisisolates enables hypermutability and is associated with extensive drug resistance. These results collectively establish that the alternative DnaQ functions in proofreading, and thus reveal that mycobacteria deploy two proofreaders to maintain replicative fidelity.
A Spatiotemporal and Machine-Learning Platform Accelerates the Manufacturing of hPSC-derived Esophageal Mucosa
Authors: Yang Ying , McCullough Carmel Grace , Seninge Lucas , Guo Lihao , Kwon Woo-Joo , Zhang Yongchun , Li Nancy Yanzhe , Gaddam Sadhana , Pan Cory , Zhen Hanson , Torkelson Jessica , Glass Ian A. ,   the Birth Defects Research Laboratory, Charville Greg , Que Jianwen , Stuart Joshua , Ding Hongxu , Oro Anthony
Published: October 2023

Human pluripotent stem cell-derived tissue engineering offers great promise in designer cell-based personalized therapeutics. To harness such potential, a broader approach requires a deeper understanding of tissue-level interactions. We previously developed a manufacturing system for the ectoderm-derived skin epithelium for cell replacement therapy. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium, despite both possessing similar stratified structure. Here we employ single cell and spatial technologies to generate a spatiotemporal multi-omics cell atlas for human esophageal development. We illuminate the cellular diversity, dynamics and signal communications for the developing esophageal epithelium and stroma. Using the machine-learning based Manatee, we prioritize the combinations of candidate human developmental signals forin vitroderivation of esophageal basal cells. Functional validation of the Manatee predictions leads to a clinically-compatible system for manufacturing human esophageal mucosa. Our approach creates a versatile platform to accelerate human tissue manufacturing for future cell replacement therapies to treat human genetic defects and wounds.
Gene expression analyses reveal differences in children’s response to malaria according to their age
Authors: Tebben Kieran , Yirampo Salif , Coulibaly Drissa , Koné Abdoulaye K. , Laurens Matthew B. , Stucke Emily M. , Dembélé Ahmadou , Tolo Youssouf , Traoré Karim , Niangaly Amadou , Berry Andrea A. , Kouriba Bourema , Plowe Christopher V. , Doumbo Ogobara K , Lyke Kirsten E. , Takala-Harrison Shannon , Thera Mahamadou A. , Travassos Mark A. , Serre David
Published: October 2023

In Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484Plasmodiumgenes. We used gene expression deconvolution to estimate the relative proportion of immune cells and parasite stages in each sample and to adjust the differential gene expression analyses. Parasitemia explained much of the variation in both host and parasite gene expression and revealed that infections with higher parasitemia had more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child’s age was also strongly correlated with gene expression variations.Plasmodium falciparumgenes associated with age suggested that older children carried more male gametocytes, while host genes associated with age indicated a stronger innate response (through TLR and NLR signaling) in younger children and stronger adaptive immunity (through TCR and BCR signaling) in older children. These analyses highlight the variability in host responses and parasite regulation duringP. falciparumsymptomatic infections and emphasize the importance of considering the children’s age when studying and treating malaria infections.

One Sentence Summary

Human andP. falciparumgene expression differs according to the infection’s parasitemia and the child’s age, highlighting an age-dependent response to malaria and complex cellular and molecular -host/parasite interactions.
Pharmacologically inducing regenerative cardiac cells by small molecule drugs
Authors: Zhou Wei , He Kezhang , Wang Chiyin , Wang Pengqi , Wang Dan , Wang Bowen , Geng Han , Lian Hong , Ma Tianhua , Nie Yu , Ding Sheng
Published: October 2023

Adult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, i.e., regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell (hESC)-derived TNNT2+CMsin vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells (ECs), and smooth muscle cells (SMCs). Importantly, similar results were observed in neonatal rat CMs bothin vitroandin vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts.
AI facilitated sperm detection in azoospermic samples for use in ICSI
Authors: Goss DM. , Vasilescu SA. , Vasilescu PA. , Cooke S. , Kim SHK. , Sacks GP. , Gardner DK , Warkiani ME.
Published: October 2023

Research question

Can artificial intelligence (AI) improve efficiency and efficacy of sperm searches in azoospermic samples?

Design

This two-phase proof-of-concept study beginning with a training phase using 8 azoospermic patients (>10000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify sperm. Secondly, side-by-side testing on 2 cohorts, an embryologist versus the AI identifying all sperm in still images (cohort 1, N=4, 2660 sperm) and then a side-by-side test with deployment of the AI model on an ICSI microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, N=4, >1300 sperm). Time taken, accuracy and precision of sperm identification was measured.

Results

In cohort 1, the AI model showed improvement in time-taken to identify all sperm per field of view (0.019±0.30 x 10-5s versus 36.10±1.18s, P<0.0001) and improved accuracy (91.95±0.81% vs 86.52±1.34%, P<0.001) compared to an embryologist. From a total of 688 sperm in all samples combined, 560 were found by an embryologist and 611 were found by the AI in <1000thof the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90±3.19s vs 168.7±7.84s, P<0.0001) and found 1396 sperm, while 1274 were found without AI, although no significant difference was observed.

Conclusions

AI-powered image analysis has the potential for seamless integration into laboratory workflows, and to reduce time to identify and isolate sperm from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.
Artificial intelligence and health equity in primary care: A qualitative study with key stakeholders
Authors: d’Elia Alexander , Gabbay Mark , Frith Lucy , Rodgers Sarah , Kierans Ciara
Published: October 2023

Artificial Intelligence (AI)-augmented interventions are currently being rolled out across primary care, but how it affects health equity remains insufficiently understood. This qualitative study addresses this gap through an ethnographical inquiry based on 32 interviews and focus groups with stakeholders including commissioners, decision makers, AI developers, researchers, GPs and patient groups involved in the implementation of AI in English primary care. We took a sociotechnical perspective in order to assess how the stakeholders can improve health equity through the implementation process of AI within the wider system. We found that regulation and policy alone cannot guarantee equitable implementation of AI but can provide a framework to enable other stakeholders to take measures to promote equity: fostering a shared understanding of the causal mechanisms of AI and health equity, how to measure health equity, and how to share data necessary for equity promotion. Further, all stakeholders need to be on board for equitable implementation, and currently innovation leaves clinicians and patients behind. Capacity building is needed to achieve this, in particular at local commissioning and clinician level. Careful implementation and pragmatically focused research are needed to make AI in primary care capable of advancing health equity.