bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertensive disorders of pregnancy increase the risk of future menopausal hot flashes in Japanese women: results from the Japan Nurses’ Health Study
Authors: Ri Moyo , Hayashi Kunihiko , Kurabayashi Takumi , Lee Jung Su , Ideno Yuki , Nagai Kazue , Yasui Toshiyuki , Kubota Toshihiro , Takamatsu Kiyoshi 
Published: October 2021

Abstract

Objective:
We aimed to investigate whether hypertensive disorders of pregnancy (HDP) are associated with problematic hot flashes in Japanese women.

Methods:
In this study, we included participants in the Japan Nurses’ Health Study who were women aged 41 to 55 years at baseline, parous, and completed a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology.

Results:
At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of HDP. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of HDP of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with HDP as compared with those without these disorders.

Conclusions:
In this prospective study, we found that women with a history of HDP have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of HDP.
Optimizing the ocular surface prior to cataract surgery
Authors: He Xu , Huang Andy S. , Jeng Bennie H. 
Published: October 2021

Purpose of review
Ocular surface disease can significantly impact the outcomes of cataract surgery. Recent studies have examined the efficacy of several new dry eye disease (DED) therapies, the extent to which epithelial debridement affects keratometric measurements in epithelial basement membrane dystrophy (EBMD) and Salzmann nodular degeneration (SND), and the predictability of refractive error following combined pterygium and cataract removal. This review aims to incorporate these newer studies in updating and further emphasizing the need for careful management and optimization of common ocular surface conditions prior to cataract surgery.

Recent findings
Common ocular surface conditions such as DED, EBMD, SND, and pterygium can cause significant irregular astigmatism and higher-order aberrations. Their resolution can substantially alter biometry measurements in preparation for cataract surgery, affecting the final visual outcome. Newer therapies for DED, such as topical lifitegrast and thermal pulsation treatment, can aid in this optimization process. If superficial keratectomy or excisions of lesions on the ocular surface are performed, sufficient healing time is needed to allow the ocular surface to reach stability prior to biometry measurements.

Summary
Ocular surface optimization is key to successful cataract surgery planning and reaching desired outcomes.
Uveitis–glaucoma–hyphema syndrome after uneventful placement of a 1-piece intraocular lens into the capsular bag
Authors: Nath Siddharth , Rai Amandeep S. 
Published: October 2021

Introduction:
Uveitis-glaucoma-hyphema (UGH) syndrome is an uncommon but serious complication of cataract surgery that occurs from chafing of the iris by an intraocular lens (IOL). UGH syndrome is typically associated with first-generation lenses, placement of an IOL in the ciliary sulcus, or bag-sulcus tilted positioning. UGH syndrome following placement of a modern 1-piece lens in the capsular bag is rare.

Patient and clinical findings:
A 55-year-old man presented with UGH syndrome 2 weeks after routine cataract surgery with in-the-bag placement of a contemporary IOL.

Diagnosis, intervention, and outcomes:
Correct positioning of the IOL was confirmed with ultrasound biomicroscopy and exploratory surgery, and IOL exchange achieved resolution of UGH sequelae.

Conclusions:
Intermittent chafing of the iris by the IOL as a result of underlying traumatic zonulopathy contributed to the development of UGH, and surgeons should be aware of this complication even with in-the-bag placement of a modern IOL.
Analgesic effect of ivabradine against inflammatory pain mediated by hyperpolarization-activated cyclic nucleotide–gated cation channels expressed on primary afferent terminals in the spinal dorsal horn
Authors: Ohashi Nobuko , Uta Daisuke , Ohashi Masayuki , Baba Hiroshi 
Published: October 2021

Abstract
Ivabradine, a hyperpolarization-activated cyclic nucleotide–gated cation (HCN) channel blocker and clinically approved bradycardic agent, has analgesic effects against neuropathic pain. Although the expression of HCN channels in the spinal dorsal horn (SDH) is augmented under inflammatory pain, spinal responses to centrally and peripherally applied ivabradine remain poorly understood. We investigated the spinal action and cellular mechanisms underlying the drug's analgesic effects against inflammatory pain using inflammatory pain model rats. Intraperitoneal and intrathecal injections of ivabradine inhibited mechanical allodynia (6 rats/dose; P < 0.05), and immunohistochemical staining showed that ivabradine suppresses the phosphorylated extracellular signal–regulated kinase activation in the SDH (6 rats/group, P < 0.01). In vitro whole-cell patch-clamp and in vivo extracellular recordings showed that direct application of ivabradine to the spinal cord decreases the mean miniature excitatory postsynaptic currents' frequency (13 rats; P < 0.01), and direct and peripheral application of ivabradine suppresses the spinal response to mechanical stimulation–evoked firing (8 rats/group, P < 0.01). Moreover, ivabradine reduces the amplitudes of monosynaptic excitatory postsynaptic currents evoked by Aδ-fiber and C-fiber stimulation (6 rats; P < 0.01) and induces a stronger inhibition of those evoked by C-fiber stimulation. These phenomena were inhibited by forskolin, an activator of HCN channels. In conclusion, spinal responses mediated by HCN channels on primary afferent terminals are suppressed by central and peripheral administration of ivabradine; the drug also exhibits analgesic effects against inflammatory pain. In addition, ivabradine preferentially acts on C-fiber terminals of SDH neurons and induces a stronger inhibition of neuronal excitability in inflammatory pain.
Comparing paclitaxel-platinum with ifosfamide-platinum as the front-line chemotherapy for patients with advanced-stage uterine carcinosarcoma
Authors: Su Ming-Hsuan , Wu Hua-Hsi , Huang Hsin-Yi , Lee Na-Rong , Chang Wen-Hsun , Lin Shih-Chieh , Chen Yi-Jen , Wang Peng-Hui 
Published: October 2021

Background:
Uterine carcinosarcoma (UCS) is a rare but highly lethal disease. Adjuvant chemotherapy is highly recommended for advanced UCS. To date, the standard chemotherapy regimen is still uncertain, although two regimens as paclitaxel-platinum (PP) and ifosfamide-platinum (IP) regimens are most commonly used. The aims of the current study attempt to compare both regimens in the management of advanced UCS patients.

Methods:
We evaluated advanced UCS patients who were treated either with PP or with IP after primary cytoreductive surgery in single institute retrospectively. The clinical-pathological parameters, recurrence, and survival were recorded.

Results:
A total of 16 patients were analyzed. Twelve patients received adjuvant PP therapy, and the remaining four patients received IP therapy. The median follow-up time was 28 months, ranging from 3.8 months to 121 months. Disease-related death occurred in 10 patients (62.5%). The median progression-free survival was 4.9 months, ranging from 3.8 months to 36.5 months in IP, and 23.1 months, ranging from 9.3 months to 121 months in PP, with statistically significant difference (p = 0.04). The median overall survival was 9.5 months (ranging from 3.8 months to 36.5 months) and 28.7 months (ranging from 10.3 months to 121 months) in IP and PP, respectively, without statistically significant difference (p = 0.06). Presence of pelvic and para-aortic lymphadenopathy and deep myometrial invasion (>1/2) were associated with worse prognosis by univariate analysis. No prognostic factor could be identified using multivariate analysis model.

Conclusion:
In the current study, due to extremely little number of subjects enrolled, the advantage of using paclitaxel-platinum regimen in the management of advanced UCS was still unclear, although a certain trend of favoring was supposed. We are looking forward to seeing more studies to identify the approximate regimen in the management of this highly lethal disease.
Characterization of Postural Sway in Patients With Persistent Postural-Perceptual Dizziness (PPPD) Using Wearable Motion Sensors
Authors: McCaslin Devin L. , Shepard Neil T. , Hollman John H. , Staab Jeffrey P. 
Published: October 2021

Objective:
To extend previous investigations of postural control in patients with persistent-postural perceptual dizziness (PPPD).

Study Design:
Case-controlled, cross-sectional, observational investigation.

Setting:
Tertiary care center.

Patients:
Fifteen patients with PPPD, 15 control volunteers.

Interventions:
Measurement of anterior-posterior (AP) and medial-lateral (ML) sway at the waist using wearable accelerometers during posturography; assessment of reach and gait.

Main Outcome Measures:
Peak-to-peak AP and ML sway displacement on the six conditions of the Sensory Organization Test (SOT); Scores on the SOT, Functional Reach Test (FRT), and Dynamic Gait Index (DGI).

Results:
Compared to control volunteers, patients with PPPD had significantly greater sway displacement at the waist in the AP direction in SOT conditions 3, 5, and 6 and in the ML direction in SOT conditions 2 and 4, resulting in significantly lower median equilibrium scores on the composite index and all six SOT conditions. Patients with PPPD had significantly lower scores on the FRT and DGI that were not correlated with SOT performance. AP sway in conditions 3 and 6 differentiated patients with PPPD from controls with high sensitivity (≥0.87) and specificity (≥0.87).

Conclusions:
This study replicated previous work showing poor SOT performance by patients with PPPD who had greater AP sway associated with visual dependence and greater ML sway in low demand conditions than controls. Patients with PPPD also performed poorer on the FRT and DGI, but lack of correlation with SOT scores suggested different mechanisms of impairment in postural control, reach, and ambulation. AP sway demonstrated potential as a diagnostic marker.
The Plane of Mesh Placement Does Not Impact Abdominal Donor Site Complications in Microsurgical Breast Reconstruction
Authors: Henn Dominic , Sivaraj Dharshan , Barrera Janos A. , Lin John Q. , Chattopadhyay Arhana , Maan Zeshaan N. , Chen Kellen , Nguyen Alan , Cheesborough Jennifer , Gurtner Geoffrey C. , Lee Gordon K. , Nazerali Rahim 
Published: October 2021

Background
Reinforcement of the abdominal wall with synthetic mesh in autologous breast reconstruction using abdominal free tissue transfer decreases the risk of bulging and herniation. However, the impact of the plane of mesh placement on donor site complications has not yet been investigated.

Methods
We performed a retrospective analysis of 312 patients who had undergone autologous breast reconstruction with muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps or deep inferior epigastric perforator (DIEP) flaps as well as polypropylene mesh implantation at the donor site. Donor site complications were compared among patients with different flap types and different mesh positions including overlay (n = 90), inlay and overlay (I-O; n = 134), and sublay (n = 88).

Results
Abdominal hernias occurred in 2.86% of patients who had undergone MS-TRAM reconstructions and in 2.63% of patients who had undergone DIEP reconstructions. When comparing patients with different mesh positions, donor site complications occurred in 14.4% of patients with overlay mesh, 13.4% of patients with I-O mesh, and 10.2% of patients with sublay mesh (P = 0.68). Abdominal hernias occurred in 4.44% of patients with overlay mesh, 2.24% of patients with I-O mesh, and 2.27% of patients with sublay mesh (P = 0.69). Multivariable logistic regression analysis did not identify a significant association between mesh position and hernia rates as well as wound complications.

Conclusions
Our data indicate that the plane of synthetic mesh placement in relation to the rectus abdominis muscle does not impact the rate of postoperative donor site complications in patients undergoing breast reconstruction with MS-TRAM or DIEP flaps.
Interrogation of T Cell-Enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism
Authors: Harbison R. Alex , Pandey Rajeev , Considine Michael , Leone Robert D. , Murray-Stewart Tracy , Erbe Rossin , Mandal Raj , Burns Mark , Casero Robert , Seiwert Tanguy , Fakhry Carole , Pardoll Drew , Fertig Elana , Powell Jonathan D. 
Published: October 2021

ABSTRACTBackgroundThe presence of cytotoxic tumor infiltrating lymphocytes (TILs) and antigen (e.g., viral, tumor neoantigens) enhances anti-tumor immunity. However, features including recruitment of tolerogenic cell types, nutrient-depletion, and the establishment of an acidic and hypoxic microenvironment diminish anti-tumor lymphocyte function. We sought to understand why the anti-tumor immune response fails despite a favorable immune profile.MethodsWe leveraged human papillomavirus-related (HPV+) head and neck squamous cell carcinomas (HNSC) to address this question given their high degree of CD8+ T cell-infiltration and virus-derived tumor-associated antigens. We evaluated expression of 2,520 metabolic genes between HPV+ HNSCs of different prognostic phenotypes. We further tested tumor-intrinsic and -extrinsic sources of polyamine (PA) gene expression based on observations from the prior analysis. We used bulk RNAseq from The Cancer Genome Atlas (TCGA; 10 different cancers) and single cell (sc) RNAseq data from two atlases to parse immune cell contributions to polyamine gene expression. We used TCGA data and an immunotherapy-treated melanoma cohort to examine survival outcomes as a function of polyamine gene set expression.ResultsPA metabolism genes were upregulated in aggressive phenotype, T cell-enriched (Thi), HPV+ HNSCs. PA synthesis and transporter gene enrichment was associated with T cell infiltration, recurrent or persistent cancer, overall survival status, primary site, molecular subtype, and MYC genomic alterations. PA synthesis and transport gene sets were more highly expressed in HPV-compared to HPV+ HNSCs. Bulk and scRNAseq data from HPV+ HNSCs demonstrated greater PA catabolism gene set expression among myeloid cells. A combined PA gene set comprised of genes involved in PA synthesis and transport was negatively correlated with cytotoxic T cell functional score across TCGA tumor types. Combined PA gene set expression was associated with greater mortality risk across five tumor types and worse survival in T cell-infiltrated, anti-PD-1-treated melanomas.ConclusionsA genomic approach leveraging T cell-infiltrated, immunogenic HPV+ HNSCs revealed an association between polyamine metabolism, anti-tumor immunity, and prognosis across several cancer types. These data address hurdles to anti-tumor immunity and immunotherapy and warrant further investigation of polyamines as a biomarker for targeted therapy in the context of a T cell-infiltrated microenvironment.
Effect of the foot-strike pattern on temporal characteristics of sagittal plane knee kinetics and kinematics during the early phase of cutting movements
Authors: Uno Yuki , Ogasawara Issei , Konda Shoji , Wakabayashi Kaito , Motoi Miyakawa , Nambo Megumi , Umegaki Kaho , Cheng Haotian , Hashizume Ken , Nakata Ken 
Published: October 2021

AbstractAnterior cruciate ligament (ACL) injury occurs soon after foot-strike. Cutting with a shallow flexed knee is considered a risk factor for ACL injury; however, how foot-strike patterns (forefoot strike [FFS] vs. rearfoot strike [RFS]) affect sagittal plane knee kinetics and kinematics after a foot-strike, is unknown. This study aimed to investigate the effect of foot-strike patterns on the temporal characteristics in sagittal plane knee kinetics and kinematics during cutting. Twenty-three males performed 45° cutting under RFS and FFS conditions. The marker position data on the lower limb, and the ground reaction force (GRF) data were collected and time-normalized (0%–100%) during the stance phase. The knee flexion angle, shank and GRF vector inclination angle relative to the global vertical axis, knee flexion/extension moment, and anterior/posterior component of GRF relative to the shank segment were calculated and compared between foot-strike patterns using statistical parametric mapping paired t-test (p<0.0071). The knee flexion angle was smaller in the RFS than in the FFS in the initial 40% of the stance phase. In the RFS condition, the GRF vector was directed anteriorly to the shank segment, and the knee extension moment was produced by GRF in 0%– 7% of the stance phase; these results were not observed in the FFS condition. These results suggest that compared to FFS, RFS induces a shallow flexed knee with an anterior-directed GRF component in the early stance phase, and might potentially provoke a risk of ACL injury.HighlightsSagittal plane knee mechanics differed between foot-strike patterns.Shallower knee flexion occurred in rearfoot strike than in forefoot strike in cutting.Ground reaction force vector directed anteriorly to shank axis in rearfoot strike.Larger Knee extension moment occurred after initial contact in rearfoot strike.Rearfoot strike had a potentially higher risk for ACL injury than forefoot strike.
APOEmissense variant R145C is associated with increased Alzheimer’s disease risk in African ancestry individuals with theAPOE ε3/ε4genotype
Authors: Guen Yann Le , Belloy Michael E. , Eger Sarah J. , Chen Annabel , Kennedy Gabriel , Thornton Timothy A. , Farrer Lindsay A. , Napolioni Valerio , He Zihuai , Greicius Michael D. 
Published: October 2021

ABSTRACTBACKGROUNDTheAPOEgene has two common missense variants that greatly impact the risk of late-onset Alzheimer’s disease (AD). Here we examined the risk of a thirdAPOEmissense variant, R145C, that is rare in European-Americans but present in 4% of African-Americans and always in phase withAPOE ε3.METHODSIn this study, we included 11,790 individuals of African and Admixed-African ancestry (4,089 cases and 7,701 controls). The discovery sample was composed of next generation sequencing data (2,888 cases and 4,957 controls), and the replication was composed of microarray data imputed on the TOPMed reference panel (1,201 cases and 2,744 contols). To assess the effect of R145C independently of theε2andε4alleles, we performed stratified analyses inε2/ε3, ε3/ε3, andε3/ε4subjects. In primary analyses, the AD risk associated with R145C was estimated using a linear mixed model regression on case-control diagnosis. In secondary analyses, we estimated the influence of R145C on age-at-onset using linear-mixed-model regression, and risk of conversion to AD using competing risk regression.RESULTSInε3/ε4-stratified meta-analyses, R145C carriers had an almost three-fold increased risk compared to non-carriers (odds ratio, 2.75; 95% confidence interval [CI], 1.84 to 4.11; P = 8.3×10−7) and had a reported AD age-at-onset almost 6 years younger (β, -5.72; 95% CI, 7.87 to -3.56; P = 2.0×10−7). Competing risk regression showed that the cumulative incidence of AD grows faster with age in R145C carriers compared to non-carriers (hazard ratio, 2.42, 95% CI, 1.81 to 3.25; P = 3.7×10−9).CONCLUSIONThe R145C variant is a potent risk factor for AD among African ancestry individuals with theε3/ε4genotype. Our findings should enhance AD risk prediction in African ancestry individuals and help elucidate the mechanisms linking the apoE protein to AD pathogenesis. The findings also add to the growing body of evidence demonstrating the importance of including ancestrally-diverse populations in genetic studies.
Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort
Authors: Spurny-Dworak B , Handschuh P , Spies M , Kaufmann U , Seiger R , Klöbl M , Konadu ME , Reed MB , Ritter V , Baldinger-Melich P , Bogner W , Kranz GS , Lanzenberger R 
Published: October 2021

AbstractSex hormones affect the GABAergic and glutamatergic neurotransmitter system as demonstrated in animal studies. However, human research has mostly been correlational in nature. Here, we aimed at substantiating causal interpretations of the interaction between sex hormones and neurotransmitter function by using magnetic resonance spectroscopy imaging (MRSI) to study the effect of gender-affirming hormone treatment (GHT) in transgender individuals.Fifteen trans men (TM) with a DSM-5 diagnosis of gender dysphoria, and 15 age-matched cisgender women (CW) underwent MRSI before and after at least 12 weeks of GHT. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (a combination of GABA and macromolecules) and Glx (a combination of glutamate and glutamine) ratios to total creatine (GABA+/tCr, Glx/tCr) were calculated in five predefined regions-of-interest (hippocampus, insula, pallidum, putamen and thalamus).Linear mixed models analysis revealed a significant measurement by gender identity effect (pcorr. = 0.048) for GABA+/tCr ratios in the hippocampus, with the TM cohort showing decreased GABA+/tCr levels after GHT compared to CW. Moreover, analysis of covariance showed a significant sex difference in insula GABA+/tCr ratios (pcorr. = 0.049), indicating elevated GABA levels in cisgender women compared to cisgender men.Our study demonstrates GHT treatment-induced GABA+/tCr reductions in the hippocampus, indicating hormone receptor activation on GABAergic cells and testosterone-induced neuroplastic processes within the hippocampus. Moreover, elevated GABA levels in the female compared to the male insula highlight the importance of including sex as factor in future MRS studies.