bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermal white adipose tissue development and metabolism: The role of transcription factor Foxn1
Authors: Walendzik Katarzyna , Kopcewicz Marta , Wiśniewska Joanna , Opyd Paulina , Machcińska‐Zielińska Sylwia , Gawrońska‐Kozak Barbara
Published: September 2023

Intradermal adipocytes form dermal white adipose tissue (dWAT), a unique fat depot localized in the lower layer of the dermis. However, recognition of molecular factors regulating dWAT development, homeostasis, and bioactivity is limited. Using Foxn1−/− and Foxn1+/+ mice, we demonstrated that epidermally expressed Foxn1 regulates dWAT development and defines the adipogenic capacity of dermal fibroblasts. In intact and post‐wounded skin, Foxn1 contributes to the initial stimulation of dWAT adipogenesis and participates in the modulation of lipid metabolism processes. Furthermore, Foxn1 activity strengthens adipogenic processes through Bmp2 and Igf2 signaling and regulates lipid metabolism in differentiated dermal fibroblasts. The results reveal the contribution of Foxn1 to dWAT metabolism, thus identifying possible targets for modulation and regulation of dWAT in physiological and pathological processes in the skin.
Efficacy of Flap-based Posterior Trunk Reconstruction after Vertebrectomy and Radiation Therapy: A Retrospective Cohort Study
Authors: Amendola Francesco , Ghiringhelli Gaia , Mela Alessandro , Miranda Sergio , Dolfato Elisa , Bulgarelli Eleonora , Diomedi Michele , Bonomi Stefano , Vaienti Luca , Luzzati Alessandro
Published: September 2023

Background:

Adjuvant radiation therapy following vertebrectomy is a major risk factor for local wound complications such as dehiscence, infection, and skin necrosis. In selected cases, well-vascularized coverage and modification of tension forces on the wound might reduce the risk of postoperative complications and reoperations. We aimed to demonstrate a reduction in general and specific complications in patients undergoing vertebral resection and flap coverage compared with vertebral resection alone.

Methods:

We retrospectively analyzed and collected data from patients diagnosed with a tumor involving the spine and requiring a total or partial posterior vertebrectomy between January 2012 and October 2022, referred to a single tertiary-level orthopedic and trauma center. We included only patients in whom primary closure of the wound was possible but judged to be under excessive tension.

Results:

A total of 145 patients underwent partial or total vertebrectomy for oncological reasons at our tertiary-level trauma hospital. Among these, 73 patients were eventually included according to the inclusion and exclusion criteria: 53 in the orthopedic group and 20 in the orthoplastic group. Considering only patients undergoing radiation therapy, the orthoplastic group showed significantly lower rates of overall complications (33% versus 69%) than the orthopedic group.

Conclusions:

Primary flap coverage, especially in patients receiving RT, reduces the risk of postoperative complications and avoids a second reconstructive operation, consequently reducing patient discomfort, length of hospital stay, and healthcare costs.
Opioid-free Pain Management after Cleft Lip Repair
Authors: Do Annie , Rorison Eve , Borucki Amber , Shibata Gail S. , Pomerantz Jason H. , Hoffman William Y.
Published: September 2023

Background:

Side effects of opioid pain management after surgical repair of cleft lips are numerous and affect postoperative course. We compared opioid versus opioid-free pain management regimens for infants who underwent cleft lip repair to evaluate the impact on postoperative recovery.

Methods:

Cleft lip repairs at our institution from December 2016 to February 2021 were retrospectively reviewed, comparing patients who received opioids to patients receiving a nonopioid pain control regimen. Data collected include length of stay, oral morphine equivalents (OME) received on day of surgery (DOS)/postoperative day (POD) 1, time to and volume of first oral feed, and Face/Legs/Activity/Cry/Consolability (FLACC) scores.

Results:

Seventy-three infants were included (47 opioid and 26 nonopioid). The opioid group received average 1.75 mg OME on DOS and 1.04 mg OME on POD1. Average DOS FLACC scores were similar between groups [1.57 ± 1.18 nonopioid versus 1.76 ± 0.94 (SD) opioid; P = 0.46]. Average POD1 FLACC scores were significantly lower for the nonopioid group (0.73 ± 1.05 versus 1.35 ± 1.06; P = 0.022). Median time to first PO (min) was similar [178 (interquartile range [IQR] 66–411) opioid versus 147 (IQR 93–351) nonopioid; P = 0.65]. Median volume of first feed (mL) was twice as high for the nonopioid group [90 (IQR 58–120) versus 45 (IQR 30–60); P = 0.003].

Conclusions:

Nonopioid postoperative pain management was more effective than opioids for pain management in infants after cleft lip repair, as evidenced by FLACC scores and increased volume of the first oral feed.
Reduction in Seroma and Other Complications with a Novel Internal Negative Pressure System in Breast Reconstruction
Authors: Paul Robert
Published: September 2023

Background:

Seroma, along with other complications, occurs as a result of poor wound healing following breast reconstructive surgery. The Interi System was developed to address the need for more effective approaches to close internal dead space and evacuate postsurgical fluid. Interi is an internal negative pressure delivery system with a unique branching manifold for broad coverage of internal tissue planes. Initial experience in a small cohort undergoing prepectoral breast reconstruction showed a clinical and statistically significant reduction in seroma and any complication versus standard drains. The purpose of this study is to report on the safety and effectiveness of Interi, compared with standard drains, in a larger patient population followed up over a longer period than our initial study.

Methods:

Data on demographics, mastectomy and reconstructive variables, postoperative complications, and manifold/drain duration were retrieved from patient records and compared between the two groups.

Results:

Interi was used in 100 patients (170 breasts) and standard drains in 100 patients (166 breasts). Groups were well matched in demographic, reconstructive, and mastectomy variables. Interi was removed significantly earlier than drains (16.5 versus 19.6 days; P < 0.0001) and was associated with a significantly lower incidence of seroma (4.1% versus 22.9%, P < 0.00001), flap revision (10.6% versus 21.7%, P = 0.006), and any complication (23.5% versus 44.0%, P = 0.0001).

Conclusions:

Interi effectively reduced dead space and evacuated fluid from internal tissue planes, thereby decreasing seroma and other complications after prepectoral breast reconstruction. As a viable alternative to standard drains, it could significantly improve patient outcomes.
Threshold effects and inflection points of flavonoid intake in dietary anti-inflammatory effects: Evidence from the NHANES
Authors: Wan Huijuan , Huang Xiongjie , Xu Yunhua , Liu Mingjiang , Wang Jiusong , Xiao Meimei , He Zhixiang , Song Jiangang , Xiao Xiangjun , Ou Jun , Tang Zetao
Published: September 2023

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007–2010, 2017–2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (−0.40 [−0.45, −0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.
Factors associated with adherence to oral HIV pre-exposure prophylaxis among female sex workers in the Mara Region, Tanzania: A 2022 cross-sectional study
Authors: Churu Mwanaidi , Kulemba Khamis , Kapesa Anthony , Kajura Alphaxard , Wilfred Diana , Basinda Namanya , Kaluvya Samwel , Mageda Kihulya Pastory
Published: September 2023

Female sex workers (FSWs) have a higher risk of acquiring human immunodeficiency virus (HIV) infection compared with the general female population. Tanzania adopted pre-exposure prophylaxis (PrEP) use for HIV-negative key populations in 2019 as a strategy to reduce HIV transmission. We aimed to identify factors associated with PrEP adherence among FSWs in Tanzania. We conducted a cross-sectional study of FSWs using oral HIV PrEP from June-July 2022 in 5 Mara Region districts. Stata software was used to analyze the quantitative data. Poor overall PrEP adherence was observed among FSWs, with adherence of 48.3% (174/360) and 43.3% (156/360) according to pill count and self-reports, respectively. Participants living with family members had 2.32 higher odds of PrEP adherence (adjusted odds ratio [aOR] = 2.32, 95% confidence interval [CI] = 1.27–42.23, P = .006) versus participants living alone or with friends. Moreover, FSWs who preferred pill packages had 1.41 higher odds of adherence (aOR = 2.43, [95% CI = 1.41–4.19, P = .001]); participants with a good perception of PrEP had 1.71 higher odds (aOR = 1.71, [95% CI = 1.01–2.91, P = .047]) of PrEP adherence. We found that living with family, pill packaging, and PrEP perception played significant roles in PrEP adherence among FSWs. Interventions to improve pill packaging, social support, and the perception of PrEP among FSWs should be intensified to increase adherence in this vulnerable population.
The effects on joint functions of biplanar distal tubercle open-wedge high tibial osteotomy: A prospective study
Authors: Zehir Sinan , Alic Taner
Published: September 2023

Distal tubercle biplanar open-wedge high tibial osteotomy (DT-BOWHTO) is a method frequently applied in the treatment of knee joint medial osteoarthritis. The aim of this study was to evaluate the radiological, clinical, and functional results of patients at 5 years after DT-BOWHTO surgery. The study included a total of 41 patients who underwent DT-BOWHTO, comprising 19 (46.3%) males and 22 (53.7%) females with a mean age of 55.54 ± 4.17 (45–63) years and mean follow-up of 66.76 ± 6.29 (60–81) months. Statistical comparisons were made of the preoperative and postoperative body mass index (BMI), modified Insall-Salvati index, Blackburn-Peel index, Kelgren-Lawrence classification (KLC), tibial slope angle, American Knee Society Functional Score (AKSFS), Clinical American Knee Society Score (CAKSS), visual analog scale (VAS) pain score, Tegner Functional Activity Score (TFAS), total corrected angular measurements (TCA), and the tibio-femoral varus angle. Compared to the preoperative values, no statistically significant difference was determined in the postoperative modified Insall-Salvati index, Blackburn-Peel index, and tibial slope angle values (P > .05), and a statistically significant difference was determined in the BMI, AKSFS, CAKSS, VAS, KLC, tibio-femoral varus angle, and TFAS values (P ≤ .001). When the preoperative and postoperative BMI values were compared in 3 groups of normal, overweight, and obese, there was found to be a statistically significant difference (P = .014). No significant correlation was determined between the BMI values and the VAS and KLC values (P > .05). No significant correlation was determined between the total corrected angular and the preoperative and postoperative pain, and clinical and functional knee scores (VAS, AKSFS, CAKSS, TFAS) (P > .05). DT-BOWHTO was seen to provide extremely good 5-year results in the knee clinical findings, pain severity, and functional results. As the patella height and tibial slope angle were not changed, this did not cause the development of osteoarthritis in the patellofemoral and tibiofemoral joints. Grafting and fixation of the tibial tubercle with additional screws in the application of DT-BOWHTO were not seen to make any additional contribution to the healing of the osteotomy line. There was no relationship between increased BMI, reduced pain, and increase in knee functions in patients who underwent DT-BOWHTO.
Global trends and frontiers of research on total disc replacement: A bibliometric analysis
Authors: Li Yanlei , Tian Jinlong , Xu Jiongnan , Ge Meng , Shao Haiyu , Zhang Jun , Zhao Tingxiao , Wang Weibin
Published: September 2023

With the increased risk of complications associated with traditional spinal fusion for the treatment of degenerative disc disease, total disc replacement (TDR) has received increasing attention in recent years. Despite the rapid development of its related research fields, its research status and the hotspot analysis are still unclear. Our goal was to identify and analyze the global research trends on TDR using bibliometric tools. All TDR data were obtained from the WoSCC. The information of research field was collected, including title, author, institutions, journals, countries, references, total citations, and years of publication for further analysis. From 1993 to 2022, a total of 1167 articles and 11,348 references were included in this field. These publications are mainly from 53 countries/regions and 174 journals, led by the United States and China. According to the citation report, the US was absolutely in the leading position in this research field. The most contribution institution and author were Sichuan University and Liu H. Spine and European Spine Journal were the most active journal on TDR research, with 205 and 118 articles. Meanwhile, they were also the most frequently cited journals. The “bone loss,” “cervical arthroplasty,” “hybrid surgery” were the most frequently cited areas of TDR research. Meanwhile, the latest research hotspots and directions were “cervical disc arthroplasty,” “7 year follow up,” “heterotopic ossification.” The scientific research on TDR has increased considerably in recent years. This study clarifies the current research status and future development trends in order to guide clinicians and researchers in the field of TDR. It can be inferred that cervical disc arthroplasty and bone loss will be the research focus in the future.
MRI measurements of brain hippocampus volume in relation to mild cognitive impairment and Alzheimer disease: A systematic review and meta-analysis
Authors: Rao Gaofeng , Gao Hui , Wang Xiaoyang , Zhang Jinchao , Ye Miaoqing , Rao Liyuan
Published: September 2023

Background:

This is the first meta-analysis conducted to compare the hippocampal volume measured by magnetic resonance imaging (MRI) in healthy normal subjects, mild cognitive impairment (MCI) and Alzheimer disease (AD), and to analyze the relationship between hippocampal volume changes and MCI and AD.

Methods:

English literatures published from January 2004 to December 2006 were extracted from PubMed, Embase, Wanfang Medical, and China National Knowledge Infrastructure databases. Statistical analysis was carried out with Stata/SE 16.0 software.

Results:

The smaller the volume of the hippocampus measured by MRI, the more severe the cognitive impairment or AD. Different MRI post-measurement correction methods have different measurement results: Left hippocampal volume measured by MRI Raw volume method is negatively correlated with MCI and AD (OR [odds ratio] = 0.58, 95%CI [confidence interval]: 0.42, 0.75) right hippocampal volume measured was not associated with MCI OR AD (OR = 0.87, 95%CI: 0.56, 1.18); left hippocampal volume measured by MRI total intracranial volume (TIV) Correction was not associated with MCI and AD (OR = 0.90, 95%CI: 0.62, 1.19), measured right hippocampal volume was not associated with MCI OR AD (OR = 0.81, 95%CI: 0.49, 1.12); left hippocampal volume measured by MRI TIV Correction was not associated with MCI and AD (OR = 0.90, 95%CI: 0.62, 1.19), measured right hippocampus volume was negatively associated with MCI and AD (OR = 0.49, 95%CI: 0.35, 0.62).

Conclusion:

The shrinkage of hippocampus volume is closely related to MCI and AD. MRI measurement of hippocampus volume is not only an auxiliary diagnostic tool for MCI and AD, but also a good prognosis assessment tool.
Risks of undernutrition and depression in hospitalized patients: A cross-sectional study
Authors: Asma Ayça , Tuncer Özge
Published: September 2023

Undernutrition in hospitalized patients is a significant healthcare burden worldwide. Depression is a major global health problem characterized by symptoms such as altered mood, loss of interest and pleasure, and impairment in cognitive and physical functions. Patients hospitalized for medical conditions have a higher risk of depression than the general population. The purpose of this study was to explore the relationship between undernutrition risk and depression risk in hospitalized patients. The design of this study was an observational cross-sectional analytic. A questionnaire form created by the investigator including sociodemographic data, dietary patterns, presence of chronic diseases and anthropometric measurements, Nutritional Risk Screening and Patient Health Questionnaire-2 were applied to the patients. All quantitative data were expressed as the median and interquartile range and qualitative data were expressed as numbers and percentage. Mann–Whitney U test and Kruskal–Wallis test were used to analyze nonparametric data; Chi-square and Fisher Exact test were used to analyze qualitative data. P < .05 was considered statistically significant. A total of 308 patients who met the criteria were reached. Undernutrition was detected in 28.6% of the participants, and depression was present in 37.3%. A statistically significant relationship was found between the risk of undernutrition and the risk of depression, with individuals without a risk of depression being found to have a lower risk of undernutrition. (P < .001). The risk of undernutrition was found to increase with advancing age. Moreover, individuals with higher values for arm muscle area, arm muscle circumference, mid-upper arm circumference, triceps skinfold thickness, calf circumference, and body mass index had a lower risk of undernutrition. No relationship was found between gender and the risk of depression. However, a statistically significant relationship was observed between age and the risk of depression, indicating that older patients had a higher risk of depression. In this study, a statistically significant relationship was found between the risk of undernutrition and the risk of depression in hospitalized patients. It was observed that the risk of undernutrition was lower in individuals without risk of depression.
Large-scale retrospective analysis of methodological factors affecting pregnancy rates after embryo transfer for in vitro fertilization
Authors: Kavrut Mustecep , Sagir Fulya Gokdagli , Atayurt Zafer
Published: September 2023

This study aimed to investigate the impact of methodological factors on pregnancy rates after embryo transfer (ET) for in vitro fertilization. This retrospective cross-sectional study was conducted between September 2020 and April 2022. A total of 2048 patients who underwent ultrasonography-guided first frozen embryo transfer (FET) or a fresh ET cycle due to infertility were included in the study. The effects of age, ET protocol (frozen or fresh), preimplantation genetic testing, number of embryos transferred (NET), and embryo fundus distance on pregnancy rate were investigated. The mean age of pregnant patients (31.51 ± 5.28) was significantly lower than that of non-pregnant patients (35.34 ± 6.39) (P < .001). Multiple regression analysis showed that women with lower age (P < .001), higher NET (P < .001), higher embryo fundus distance (P < .001), FET (P < .001), and preimplantation genetic testing (P = .012) had a significantly higher likelihood of pregnancy. Appropriate transfer depth, younger age, euploid embryo transfer, FET, and a higher NET can increase the likelihood of pregnancy. However, multiple factors must be considered when deciding the best protocol for a particular patient, including patient preference, costs and timing.
Modified lateral approach combined with medial percutaneous approach versus triceps tongue-shaped flap approach and bilateral triceps brachii approach for pin fixation in treatment of irreducible displaced pediatric supracondylar humeral fractures
Authors: Da Hu , Zhou Liang , Xi Qiao-Yun , Xu Chang-Ming
Published: September 2023

To evaluate the clinical outcomes of the modified lateral approach combined with the medial percutaneous approach (MLACMPA) versus the triceps tongue-shaped flap approach (TTSFA) and the bilateral triceps brachii approach (BTBA) in the treatment of irreducible displaced supracondylar humeral fractures (SHFs) in children. Between March 2000 and July 2022, a total of 135 children who underwent open reduction and Kirschner wire cross internal fixation for irreducible displaced SHFs caused by trauma were retrospectively analyzed. According to the surgical approach, the patients were assigned to the TTSFA group (n = 36), the BTBA group (n = 40) and the MLACMPA group (n = 59). The duration of surgery, intraoperative blood loss, incision length, and elbow range of motion were compared. The 3 groups were similar in terms of mean age, sex distribution, and time from injury to operation. The duration of surgery, intraoperative blood loss, incision length and postoperative elbow range of motion in the MLACMPA group were significantly superior to those in the TTSFA group and BTBA group (P < .05). Compared the use of the TTSFA or the BTBA, using the MLACMPA for pin fixation in the treatment of irreducible displaced pediatric SHFs could significantly shorten the duration of surgery, reduce the operation trauma, facilitate earlier functional exercise of joints after operation and yield better elbow function.
Ketogenic Diets in Children With Intractable Epilepsy and its Effects on Gastrointestinal Function, Gut Microbiome, Inflammation, and Quality of Life
Authors: Menzies Jessica , Sundararaj Alamelu , Cardamone Michael , McHarg Alexandra , Leach Steven , Krishnan Usha
Published: September 2023

Objectives:

The ketogenic diet (KD) is a treatment for children with intractable epilepsy (IE), can cause gastrointestinal symptoms, and have an adverse effect on growth, nutrition and quality of life (QOL). This study investigated the extent of these side effects by comparing children with IE on KDs to their counterparts on normal diets.

Methods:

Patients with IE were categorized into patients with KD or control groups. Gastrointestinal side effects and QOL were assessed using the PedsQL Gastrointestinal Symptoms Module. Cross sectional growth, gut microbiome compositions, and inflammation levels were also analyzed.

Results:

Fourteen patients on the KD and 13 control patients were enrolled. Patients had been on KD for a median duration of 15 months (interquartile range: 9.8–60 months). The patients on the KD reported a trend to lower total gastrointestinal symptoms scores (more symptoms) compared to control patients, at 71.1 and 84.9, respectively (P = 0.06, not significant). Patients on the KD had significantly lower QOL scores compared to control patients (P = 0.01). Patients on the KD were found to have consistently lower median height/length, weight, and body mass index z scores compared to the controls although these were not statistically significant. Patients on the KD had a lower microbial diversity, Both groups had a normal level of S100A12, a marker of gut inflammation.

Conclusions:

Patients on the KD reported a trend to more gastrointestinal symptoms and more QOL concerns compared to controls. Although microbial differences were noted in patients on the KD, this did not result in detectable gut inflammation.
Serial 68Ga-FAPI PET/CT After Treatment of Immunoglobulin G4-Related Pancreatitis and Retroperitoneal Fibrosis
Authors: Cho Eunae , Park Chang Hwan , Kim Jahae , Kim Kangbin , Kim Sung Sun
Published: September 2023

Immunoglobulin G4 (IgG4)–related disease is a fibroinflammatory condition involving diverse organs. We report a case of IgG4-related pancreatitis and retroperitoneal fibrosis with serial 68Ga-FAPI PET/CT scans after treatment. A 64-year-old man presented with left flank and epigastric pain. Laboratory, abdominal CT, and 68Ga-FAPI PET/CT findings were suggestive of IgG4-related pancreatitis and retroperitoneal fibrosis. Histology of the pancreas confirmed IgG4-related pancreatitis. The follow-up PET/CT scans after treatment with steroid therapy showed regression of 68Ga-FAPI uptake in the pancreas and periureteral soft tissue. The changes on 68Ga-FAPI PET/CT scans were much more prominent compared with the CT scans.
Unexpected Axillary Lymph Node Uptake During Lower-Limb Lymphoscintigraphy in a Case With Vulvar Lymphangioma Circumscriptum
Authors: Soydas-Turan Basak , Tuncel Murat
Published: September 2023

Lymphoscintigraphy is a safe, minimally invasive, and well-established imaging modality for evaluating lymphatic drainage in patients with suspected lymphedema. We report a case of an 8-year-old girl with lymphangioma circumscriptum of the labium majora. She was referred to lymphoscintigraphy for swelling of the lower extremities. Scintigraphy showed widespread dermal backflow at bilateral lower limbs, aberrant uptake in the abdominal lymph nodes, and unexpected uptake in the right axillary lymph nodes.
Striatal Hyperperfusion Observed in Dual-Phase 18F-FP-CIT PET Imaging of Hyperglycemic Chorea
Authors: Kim Yoon Seob , Park Don Gueu , Shin In Ja , An Young Sil , Yoon Jung Han
Published: September 2023

A 76-year-old woman with a history of diabetes mellitus presented with right-side dominant generalized chorea. At presentation, her blood glucose level was 500 mg/dL with an HbA1C of 11%. Because the patient had been on levodopa treatment from her primary physician, a dual-phase 18F-FP-CIT PET scan was performed. The early-phase images showed increased perfusion in the bilateral striatum, and the delayed-phase images revealed decreased uptake in the left caudate. Hyperperfusion in the striatum may indicate the acute phase of hyperglycemic chorea. This image illustrates the advantage of adding early-phase scans in 18F-FP-CIT PET in differentiating various hyperkinetic and hypokinetic disorders.
Detailed Assessment of 18F-THK5351 Distribution Pattern in the Midbrain: Comparison With Progressive Supranuclear Palsy and Corticobasal Syndrome
Authors: Ishibashi Kenji , Kurihara Masanori , Ihara Ryoko , Higashihara Mana , Iwata Atsushi , Ishii Kenji
Published: September 2023

Background

18F-THK5351 PET is used to image ongoing astrogliosis by estimating monoamine oxidase B levels. 18F-THK5351 preferentially accumulates around the substantia nigra (SN) and periaqueductal gray (PG) in the midbrain under healthy conditions and exhibits a “trimodal pattern.” In progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), the midbrain 18F-THK5351 uptake can be increased by astrogliosis, collapsing the “trimodal pattern.” We aimed to elucidate cases in which the “trimodal pattern” collapses in PSP and CBS.

Patients and Methods

Participants in the PSP (n = 11), CBS (n = 17), Alzheimer disease (n = 11), and healthy control (n = 8) groups underwent 18F-THK5351 PET. Volumes of interest (VOIs) were placed on the SN, PG, and their midpoints. The midbrain uptake ratio (MUR) was calculated to assess the trimodal pattern as follows: MUR = (VOI value on the midpoint)/(VOI value on the SN and PG). Approximately, the trimodal pattern can be identified at MUR <1 but not at MUR >1.

Results

Compared with the healthy control group, MUR significantly increased in the PSP (P < 0.01) and CBS (P < 0.01) groups, but was unchanged in the Alzheimer disease group (P = 0.10). In the PSP group, all patients, including 2 with mild symptoms and a short disease duration, showed MUR >1. In the CBS group, MUR varied widely.

Conclusions

In PSP, the trimodal pattern can collapse even in the early phase when symptoms are mild. In CBS, the trimodal pattern may or may not collapse depending on the underlying pathology.
Evaluation of Anastomosis Efficiency in Arteriovenous Shunts Created by Using Hand-Sewn Microsurgery and Microvascular Anastomotic Coupler Device
Authors: Ceran Fatih , Kuvat Samet V. , Ozel Asuman , Pilanci Ozgur , Kayalar Nihan , Bilgi Esra , Yalcin Senay
Published: September 2023

Objective:

Microsurgery has made great contributions to the advancement of surgery. In parallel with the developments in microsurgery, various techniques have been developed to perfect the technique. Microvascular anastomotic coupler device (MACD) is one of these techniques. The aim of the study was to evaluate the effectiveness of anastomoses created by using hand-sewn microsurgery (HSM) and MACD.

Methods:

Twenty male Sprague-Dawley rats weighing 250 to 300 g were divided into 2 groups randomly. Arteriovenous shunt was performed between carotid artery and internal jugular vein with the principles of HSM in the first group (n=10) and by using the 1-mm anastomotic microvascular device in the second group (n=10). Groups were evaluated for anastomose time, success of anastomosis, thrombosis formation, color Doppler ultrasonography, and histopathological features.

Results:

Anastomotic time was faster with the coupler device compared with HSM technique. Flow rates were found significantly higher in the MACD group. Endothelialization and wall integrity rates were better in MACD group.

Conclusions:

Microvascular anastomotic coupler device is faster than HSM. High quality and durability of vascularization, insignificant foreign body reactions are histopathological advantages of MACD.
Incidence of Sinusitis Postoperatively in Orthognathic Surgery: A Systematic Review and Meta-Analysis
Authors: Talugula Snehitha , Johnson Vickie , Zhao Linping , Patel Pravin , Lee Victoria
Published: September 2023

Maxillary osteotomies as a component of orthognathic surgery disrupt the normal anatomy and function of the sinus. The osteotomy with advancement of the inferior component of the sinus leaves a bony and mucosal opening in the sinus. Immediately after surgery, nasal drainage is impeded because of intranasal swelling. Acute and chronic maxillary sinusitis would be expected; however, its incidence as an expected complication is not well documented. A systematic review and meta-analysis was completed using PubMed to determine the incidence of sinusitis after maxillary orthognathic surgery. Studies were reviewed by two authors, and incidence data were extracted. Two hundred six articles were identified with 24 meeting the criteria for analysis. The incidence of sinusitis was based on 4213 participants who had undergone orthognathic surgery. Twenty-three studies reported a total number of sinusitis cases, and the results demonstrated a pooled incidence of 3.3% (95% confidence interval: 1.77, 6.06). One study did not report a total number of cases but reported chronic sinusitis survey-duration-based and Lund-Mackay scores. These scores, respectively, worsened from 7.6 to 14.8 and from 1.58 to 2.90 postoperatively. Despite the variability of maxillary surgery, the surgical technique, and the postoperative management, the incidence is low but sinusitis does occur. Prospective studies with validated questionnaires within the context of a specific protocol may further elucidate the causality of sinusitis. Further, patients with sinonasal symptoms postsurgery should be encouraged to consult with an otolaryngologist to ensure prompt treatment.
The Effect of Denosumab in Elderly Patients Regarding Bone Density and Fracture Risk
Authors: Yoon Sung-Hyun , Kim Karam , Kim Ki-Choul
Published: September 2023

Background: With an aging population, the importance of treating and diagnosing osteoporosis is increasing. Osteoporosis, previously known as a resorptive change primarily related to endocrinological mechanisms, is also being approached as a phenomenon of senile change. Denosumab is gaining popularity among osteoporosis medications due to its ability to increase bone mineral density (BMD) and the economic benefit arising from the 6-month cycle. In line with previous literature, this study aimed to examine the BMD-augmenting effect of denosumab through which it reduces fracture risk in individuals aged over 80 years.Methods: We reviewed patients who received denosumab between 2018 and 2022 with a minimum clinical observation period of 12 months. BMD was measured every 12 months, and patients were classified per their period of denosumab use. Fracture risk was evaluated using the fracture risk assessment tool (FRAX) and fracture incidence during the observation period were assessed.Results: Among 155 patients, a significant increase in BMD was observed at 3 sites: the lumbar spine, femoral neck, and total hip (p<0.001, p<0.001, and p=0.001, respectively). The patients were divided according to the length of clinical follow-up they received, and similar results were found in all subgroups. Fracture risk assessment was performed using FRAX and the incidence of fracture events during follow-up. FRAX significantly decreased in all subgroups except those who received 24 months of follow-up (p=0.003, p=0.41, p=0.001 in the 12, 24, and ≥36 months groups, respectively).Conclusions: Denosumab use resulted in long-term BMD increase and reduced fracture risk in individuals aged 80 and above.
Black Bone Disease: Ochronotic Arthritis Detected during Knee Arthroplasty
Authors: Kang Ho Won , Kim Minsub , Oh Jin-Young , Youn Changhyun
Published: September 2023

Alkaptonuria is an extremely rare autosomal recessive metabolic disorder characterized by dark urine, ochronosis, and arthritis of the spine and major joints. We report a case of ochronotic arthritis observed during total knee replacement surgery in a 65-year-old male patient with no relevant medical history. Based on a literature review, this is the first case of ochronotic arthritis reported in Korea.
Mortality and malformation effects of boric acid against larval stage ofAedes aegypti(Culicidae: Diptera)
Authors: Sharawi Somia Eissa
Published: September 2023

Mosquitoes, the disquieting insect, can transmit pathogens more than any other insect, and they can cause fatal diseases to both humans and animals in their environment. With the increasing problem of pesticide resistance spreading in the field, substantial efforts are being made at the international level to develop environmental insecticides to reduce these mosquito populations or limit their potential to transmit disease. In this preliminary study, mortality and malformation effects of seven concentrations (700, 1000, 1200, 1500, 2000, 2500, and 3000 ppm) of boric acid were evaluated against the 4thlarval stage ofAedes aegyptiafter 24 h of exposure. Malformed and dead larvae were photographed under the microscope with a digital camera connected to a computer stereo-dissecting microscope. Our results showed that the lethal concentrations (LC50and LC90) were 1312.49 and 2578.26, respectively. Also, the results showed malformation effects against treated larvae with boric acid compared to the control group. These malformations manifested in albino pupa, Pigmentation, Larval-pupal intermediate, Black coloration at the posterior end, Opaque swelling on the thorax, Segment contraction, Deformed cuticles, black coloration at the posterior end, and nick elongation. Boric acid is less toxic than synthesized insecticides, and in low concentrations, it causes mortality and malformation effects against larval stages ofA. aegypti. Further, the use of boric acid as a safe method for controlling larval stages ofA. aegyptican be recommended as it is available, cost-effective, and less harmful to humans, animals, and the environment.
Machine learning and phylogenetic analysis allow for predicting antibiotic resistance inM. tuberculosis
Authors: Yurtseven Alper , Buyanova Sofia , Agrawal Amay Ajaykumar , Bochkareva Olga O. , Kalinina Olga V.
Published: September 2023

Antimicrobial resistance (AMR) poses a significant global health threat, and an accurate prediction of bacterial resistance patterns is critical for effective treatment and control strategies. In recent years, machine learning (ML) approaches have emerged as powerful tools for analyzing large-scale bacterial AMR data. However, ML methods often ignore evolutionary relationships among bacterial strains, which can greatly impact performance of the ML methods, especially if resistance-associated features are attempted to be detected. Genomewide association studies (GWAS) methods like linear mixed models accounts for the evolutionary relationships in bacteria, but they uncover only highly significant variants which have already been reported in literature. In this work, we introduce a novel phylogeny-related parallelism score (PRPS), which measures whether a certain feature is correlated with the population structure of a set of samples. We demonstrate that PRPS can be used, in combination with SVM- and random forest-based models, to reduce the number of features in the analysis, while simultaneously increasing models’ performance. We applied our pipeline to publicly available AMR data from PATRIC database forMycobacterium tuberculosisagainst six common antibiotics. Using our pipeline, we re-discovered known resistance-associated mutations as well as new candidate mutations which can be related to resistance and not previously reported in the literature.
Analysis of emergent bivalent antibody binding identifies the molecular reach as a critical determinant of SARS-CoV-2 neutralisation potency
Authors: Huhn Anna , Nissley Daniel Allen , Wilson Daniel B , Kutuzov Mikhail A , Donat Robert , Tan Tiong Kit , Zhang Ying , Barton Michael I , Liu Chang , Dejnirattisai Wanwisa , Supasa Piyada , Mongkolsapaya Juthathip , Townsend Alain , James William S , Screaton Gavin , van der Merwe Philip Anton , Deane Charlotte , Isaacson Samuel , Dushek Omer
Published: September 2023

Key functions of antibodies, such as viral neutralisation, depend on bivalent binding but the factors that influence it remain poorly characterised. Here, we develop and employ a new bivalent model to mechanistically analyse binding between >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces. Our method reproduces the monovalent on/off-rates and enables measurements of the bivalent on-rate and the molecular reach: the maximum antigen separation that supports bivalent binding. We find large variations in these parameters across antibodies, including variations in reach (22-46 nm) that exceed the physical antibody size (~15 nm) due to the antigen size. The bivalent model integrates all parameters, including reach and antigen density, to predict an emergent binding potency for each antibody that matches their neutralisation potency. Indeed, antibodies with similar monovalent affinities to the same RBD-epitope but with different reaches display differences in emergent bivalent binding that match differences in their neutralisation potency. Together, our work highlights that antibodies within an isotype class binding the same antigen can display differences in molecular reach that can substantially modulate their emergent binding and functional properties.
High Throughput Tomography (HiTT) on EMBL Beamline P14 on PETRA III
Authors: Albers Jonas , Nikolova Marina , Svetlove Angelika , Darif Nedal , Lawson Matthew J. , Schneider Thomas R. , Schwab Yannick , Bourenkov Gleb , Duke Elizabeth
Published: September 2023

Here we present High-Throughput Tomography (HiTT), a fast and versatile phase-contrast imaging platform for life-science samples on the EMBL beamline P14 at DESY in Hamburg, Germany. We use a high photon flux undulator beamline to perform tomographic phase contrast acquisition in about two minutes which is linked to an automated data processing pipeline that delivers a 3D reconstructed data set less than a minute and a half after the completion of the X-ray scan. Combining this workflow with a sophisticated robotic sample changer enables the streamlined collection and reconstruction of X-ray imaging data from potentially hundreds of samples during a beamtime shift. HiTT permits optimal data collection for many different samples and makes possible the imaging of large sample cohorts thus allowing population studies to be attempted. We demonstrate the successful application of HiTT on various soft tissue samples in both liquid (hydrated and also dehydrated) and paraffin embedded preparations. Furthermore, we demonstrate the feasibility of HiTT to be used as a targeting tool for volume electron microscopy (vEM), as well as using HiTT to study plant morphology. We also show how the high throughput nature of the work has allowed large numbers of “identical” samples to be imaged to enable statistically relevant sample volumes to be studied.

Synopsis

We present HiTT – high throughput tomography – a propagation based phase contrast X-ray imaging technique which can visualise 1 mm3biological samples of various types at high resolution. The 3D reconstructions of the imaged volumes are calculated automatically once data collection is complete. The entire process from pressing start on data collection to viewing the final data takes less than 3 minutes. This speed in combination with the use of the automated sample changer to exchange the samples truly enables high throughput X-ray imaging for the first time.
An emergent biosynthetic pathway to essential amino acids by metabolic metathesis
Authors: Rivollier Julie , Gosling Sandrine , Pezo Valérie , Heck Marie-Pierre , Marlière Philippe
Published: September 2023

An experimental approach to implanting foreign chemical reactions into living cells is to select for the catalytic production of a vital building-block such as an amino acid. Alkene metathesis is unknown in extant biochemistry, but is emerging as a new type of reaction to be catalyzed by protein enzymes. Here we show how the alkenic amino acid vinylglycine can be generated in a biocompatible reaction from 5-allyloxy-2-amino-pent-3-enoate (APE) by ring-closing metathesis catalyzed by a standard Hoveyda-Grubbs catalyst. The vinylglycine produced in situ is then used as a precursor of isoleucine and methionine, thus allowing the growth of strains of Escherichia coli requiring these essential amino acids. The robust nutritional screen we have developed paves the way for the directed evolution of genetically encoded metathesis enzymes and the chemical elaboration of metathesis coenzymes.
An economic evaluation of two cervical screening algorithms in Belgium: HR-HPV primary compared to HR-HPV and liquid-based cytology (LBC) co-testing
Authors: Dombrowski Caroline , Bourgain Claire , Ma Yixuan , Meiwald Anne , Pinsent Amy , Weynand Birgit , Turner Katy ME , Huntington Susie , Adams Elisabeth J , Bogers Johannes , Croes Romaric , Sahebali Shaira
Published: September 2023

Objective

To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium 1) high-risk human papillomavirus (HR-HPV) primary screening and 2) HR-HPV and liquid-based cytology (LBC) co-testing.

Methods

A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577,846 women aged 25 – 64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted.

Results

The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65,588,573 and €58,775,083 respectively for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13,173 more colposcopies, 67,731 more HR-HPV tests and 477,020 more LBC tests. Co-testing identified 2,351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1,602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary.

Conclusion

In Belgium, a co-testing testing algorithm could increase cervical precancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies.
Long-term disgust habituation with limited generalisation in care home workers
Authors: Edgar Charlotte , Chan Faye , Armstrong Thomas , Dalmaijer Edwin S.
Published: September 2023

Countless workers handle bodily effluvia and body envelope violations every working day, and consequentially face deeply unpleasant levels of disgust. Understanding if and how they adapt can help inform policies to improve worker satisfaction and reduce staff turnover. So far, limited evidence exist that self-reported disgust is reduced (or lower to begin with) among those employed in high-disgust environments. However, it is unclear if this is due to demand effects or translates into real behavioural changes. Here, we tested healthcare assistants (N=32) employed in UK care homes and a control sample (N=50). We replicated reduced self-reported pathogen disgust sensitivity in healthcare workers compared to controls. We also found it negatively correlated with career duration, suggesting long-term habituation. Furthermore, we found that healthcare assistants showed no behavioural disgust avoidance on a web-based preferential looking task (equivalent to eye tracking). Surprisingly, this extended to disgust elicitors found outside care homes, suggesting generalisation of disgust habituation. While we found no difference between bodily effluvia (core disgust) and body envelope violations (gore disgust), generalisation did not extend to other domains: self-reported sexual and moral disgust sensitivity were not different between healthcare assistants and the control group, nor was there a correlation with career duration. In sum, our work confirms that people in high-frequency disgust employment are less sensitive to pathogen disgust. Crucially, we provide preliminary evidence that this is due to a process of long-term habituation with generalisation to disgust-elicitors within the pathogen domain, but not beyond it.