bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of BTB Dynamics in Spermatogenesis—Insights From the Adjudin Model
Authors: Mao Bai-Ping , Li Linxi , Yan Ming , Ge Renshan , Lian Qingquan , Cheng C Yan 
Published: August 2019

Abstract
During spermatogenesis, cell organelles, and germ cells, most notably haploid spermatids, are transported across the seminiferous epithelium so that fully developed spermatids line-up at the edge of the tubule lumen to undergo spermiation at stage VIII of the cycle. Studies have suggested that the microtubule (MT)-based cytoskeleton is necessary to support these cellular events. However, the regulatory molecule(s) and underlying mechanism(s) remain poorly understood. Herein, we sought to better understand this event by using an adjudin-based animal model. Adult rats were treated with adjudin at low-dose (10 mg/kg b.w.) which by itself had no notable effects on spermatogenesis. Rats were also treated with low-dose adjudin combined with overexpression of 2 endogenously produced blood-testis barrier (BTB) modifiers, namely rpS6 (ribosomal protein S6, the downstream signaling protein of mammalian target of rapamycin complex 1 [mTORC1]) and F5-peptide (a biological active peptide released from laminin-γ3 chain at the Sertoli-spermatid interface) versus the 2 BTB modifiers alone. Overexpression of these 2 BTB modifiers in the testis was shown to enhance delivery of adjudin to the testis, effectively inducing disruptive changes in MT cytoskeletons, causing truncation of MT conferred tracks that led to their collapse across the epithelium. The net result was massive germ cell exfoliation in the tubules, disrupting germ cell transport and cell adhesion across the seminiferous epithelium that led to aspermatogenesis. These changes were the result of disruptive spatial expression of several MT-based regulatory proteins. In summary, MT cytoskeleton supported by the network of MT regulatory proteins is crucial to maintain spermatogenesis.
A Comparison of Intracochlear Pressures During Ipsilateral and Contralateral Stimulation With a Bone Conduction Implant
Authors: Mattingly Jameson K. , Banakis Hartl Renee M. , Jenkins Herman A. , Tollin Daniel J. , Cass Stephen P. , Greene Nathaniel T. 
Published: August 2019

Objectives:To compare contralateral to ipsilateral stimulation with percutaneous and transcutaneous bone conduction implants.Background:Bone conduction implants (BCIs) effectively treat conductive and mixed hearing losses. In some cases, such as in single-sided deafness, the BCI is implanted contralateral to the remaining healthy ear in an attempt to restore some of the benefits provided by binaural hearing. While the benefit of contralateral stimulation has been shown in at least some patients, it is not clear what cues or mechanisms contribute to this function. Previous studies have investigated the motion of the ossicular chain, skull, and round window in response to bone vibration. Here, we extend those reports by reporting simultaneous measurements of cochlear promontory velocity and intracochlear pressures during bone conduction stimulation with two common BCI attachments, and directly compare ipsilateral to contralateral stimulation.Methods:Fresh–frozen whole human heads were prepared bilaterally with mastoidectomies. Intracochlear pressure (PIC) in the scala vestibuli (PSV) and tympani (PST) was measured with fiber optic pressure probes concurrently with cochlear promontory velocity (VProm) via laser Doppler vibrometry during stimulation provided with a closed-field loudspeaker or a BCI. Stimuli were pure tones between 120 and 10,240 Hz, and response magnitudes and phases forPICandVPromwere measured for air and bone conducted sound presentation.Results:Contralateral stimulation produced lower response magnitudes and longer delays than ipsilateral in all measures, particularly for high-frequency stimulation. Contralateral response magnitudes were lower than ipsilateral response magnitudes by up to 10 to 15 dB above ~2 kHz for a skin-penetrating abutment, which increased to 25 to 30 dB and extended to lower frequencies when applied with a transcutaneous (skin drive) attachment.Conclusions:Transcranial attenuation and delay suggest that ipsilateral stimulation will be dominant for frequencies over ~1 kHz, and that complex phase interactions will occur during bilateral or bimodal stimulation. These effects indicate a mechanism by which bilateral users could gain some bilateral advantage.
Lupus nephritis: challenges and progress
Authors: Davidson Anne , Aranow Cynthia , Mackay Meggan 
Published: August 2019

Purpose of review
The management of lupus nephritis remains unsatisfactory due to insufficiently effective treatment regimens and the dearth of reliable predictors of disease onset or progression to guide individualized therapeutic decisions. This review summarizes new findings related to lupus nephritis over the last 18 months and discusses clinical needs that should be considered to advance trials of mechanism-based therapeutic strategies.

Recent findings
Collaborative teams are addressing how to improve disease definitions and are developing predictive models for disease onset, disease response and risk of flare in individual patients. More attention is being paid to clinical trial design. Advanced technologic approaches are allowing the analysis of small amounts of human tissue and urine in unprecedented detail so as to discover new pathogenic mechanisms and identify disease biomarkers. Novel therapies continue to be tested in disease models and include new strategies to protect renal tissue from cell damage and fibrosis.

Summary
The collaborative efforts of patients, clinical and translational researchers, the pharmaceutical industry and funding sources are needed to advance therapies for lupus nephritis. Specialized clinical centers can then deliver optimal and more personalized patient care that will improve patient outcomes.
Highlighting a Potential Pitfall: Positive Treponema pallidum Immunohistochemical Stain in a Patient Without Syphilis
Authors: Pettit Cory , McMurray Stacy , Randall Milton Barry , Jones Allison , Fisher Kristopher 
Published: August 2019

Abstract:
The Treponema pallidum antibody immunohistochemical (IHC) stain has improved our ability to detect the organism histologically. We present a case of a man with genital condyloma acuminatum with a positive T. pallidum IHC stain but negative T. pallidum serologies and no syphilitic symptoms. It has been shown that the T. pallidum antibody IHC can cross-react, staining other spirochetes, including Borrelia burgdorferi and the Brachyspira family of intestinal spirochetes. Because of the proximity of our patient's lesions to the anus, and the persistently negative T. pallidum serologies, we believe nontreponemal spirochetes colonized the condyloma, giving a false-positive T. pallidum IHC. This cross-reactivity is a potential diagnostic pitfall and is important for the dermatopathologist to recognize, thereby avoiding false diagnosis of syphilis.
Reconstruction of the mandible for osteoradionecrosis
Authors: Haroun Kareem , Coblens Orly M. 
Published: August 2019

Purpose of review
To describe current standard of care for osteoradionecrosis (ORN) of the mandible and report possible future trends.

Recent findings
Cutting guides may be used to reduce surgical time and possibly improve outcomes. There has also been recent investigation into the use of pentoxifylline and tocopherol or pentoxifylline, tocopherol and clodronate (a well known conservative medial regime) as a prevention for development of ORN after dental extractions and the first randomized controlled study is upcoming. Augmented reality has shown promise as a comparable and inexpensive possible alternative to cutting guides.

Summary
Current standard of care involves conservative/supportive therapy with antioxidants, antibiotics, steroids, and pain control for low-grade ORN with surgery reserved for high-grade/progressive ORN with refractory to conservative therapy and with significant oral dysfunction.
The Greater Omentum—A Vibrant and Enigmatic Immunologic Organ Involved in Injury and Infection Resolution
Authors: Wang Andrew W. , Prieto James M. , Cauvi David M. , Bickler Stephen W. , De Maio Antonio 
Published: August 2019

ABSTRACT
Once thought of as an inert fatty tissue present only to provide insulation for the peritoneal cavity, the omentum is currently recognized as a vibrant immunologic organ with a complex structure uniquely suited for defense against pathogens and injury. The omentum is a source of resident inflammatory and stem cells available to participate in the local control of infection, wound healing, and tissue regeneration. It is intimately connected with the systemic vasculature and communicates with the central nervous system and the hypothalamic pituitary adrenal axis. Furthermore, the omentum has the ability to transit the peritoneal cavity and sequester areas of inflammation and injury. It contains functional, immunologic units commonly referred to as “milky spots” that contribute to the organ's immune response. These milky spots are complex nodules consisting of macrophages and interspersed lymphocytes, which are gateways for the infiltration of inflammatory cells into the peritoneal cavity in response to infection and injury. The omentum contains far greater complexity than is currently conceptualized in clinical practice and investigations directed at unlocking its beneficial potential may reveal new mechanisms underlying its vital functions and the secondary impact of omentectomy for the staging and treatment of a variety of diseases.
The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status
Authors: Margonis Georgios Antonios , Amini Neda , Buettner Stefan , Kim Yuhree , Wang Jaeyun , Andreatos Nikolaos , Wagner Doris , Sasaki Kazunari , Beer Andrea , Kamphues Carsten , Morioka Daisuke , Løes Inger Marie , Imai Katsunori , He Jin , Pawlik Timothy M. , Kaczirek Klaus , Poultsides George , Lønning Per Eystein , Burkhart Richard , Endo Itaru , Baba Hideo , Mischinger Hans Joerg , Aucejo Federico N. , Kreis Martin E. , Wolfgang Christopher L. , Weiss Matthew J. 
Published: August 2019

Objective:
To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status.

Background:
Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors.

Methods:
Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status.

Results:
277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38).

Conclusions:
This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.
Patient Factors Associated With Opioid Consumption in the Month Following Major Surgery
Authors: Larach Daniel B. , Sahara Michael J. , As-Sanie Sawsan , Moser Stephanie E. , Urquhart Andrew G. , Lin Jules , Hassett Afton L. , Wakeford Joseph A. , Clauw Daniel J. , Waljee Jennifer F. , Brummett Chad M. 
Published: August 2019

Objective:
The aim of this study was to determine preoperative patient characteristics associated with postoperative outpatient opioid use and assess the frequency of postoperative opioid overprescribing.

Summary Background Data:
Although characteristics associated with inpatient opioid use have been described, data regarding patient factors associated with opioid use after discharge are lacking. This hampers the development of individualized approaches to postoperative prescribing.

Methods:
We included opioid-naïve patients undergoing hysterectomy, thoracic surgery, and total knee and hip arthroplasty in a single-center prospective observational cohort study. Preoperative phenotyping included self-report measures to assess pain severity, fibromyalgia survey criteria score, pain catastrophizing, depression, anxiety, functional status, fatigue, and sleep disturbance. Our primary outcome measure was self-reported total opioid use in oral morphine equivalents. We constructed multivariable linear-regression models predicting opioids consumed in the first month following surgery.

Results:
We enrolled 1181 patients; 1001 had complete primary outcome data and 913 had complete phenotype data. Younger age, non-white race, lack of a college degree, higher anxiety, greater sleep disturbance, heavy alcohol use, current tobacco use, and larger initial opioid prescription size were significantly associated with increased opioid consumption. Median total oral morphine equivalents prescribed was 600 mg (equivalent to one hundred twenty 5-mg hydrocodone pills), whereas median opioid consumption was 188 mg (38 pills).

Conclusions:
In this prospective cohort of opioid-naïve patients undergoing major surgery, we found a number of characteristics associated with greater opioid use in the first month after surgery. Future studies should address the use of non-opioid medications and behavioral therapies in the perioperative period for these higher risk patients.
Prospective evaluation and comparison of the predictive ability of different frailty scores to predict outcomes in geriatric trauma patients
Authors: Hamidi Mohammad , Haddadin Zaid , Zeeshan Muhammad , Saljuqi Abdul Tawab , Hanna Kamil , Tang Andrew , Northcutt Ashley , Kulvatunyou Narong , Gries Lynn , Joseph Bellal 
Published: August 2019

BACKGROUND
Different frailty scores have been proposed to measure frailty. No study has compared their predictive ability to predict outcomes in trauma patients. The aim of our study was to compare the predictive ability of different frailty scores to predict complications, mortality, discharge disposition, and 30-day readmission in trauma patients.

METHODS
We performed a 2-year (2016–2017) prospective cohort analysis of all geriatric (age, >65 years) trauma patients. We calculated the following frailty scores on each patient; the Trauma-Specific Frailty Index (TSFI), the Modified Frailty Index (mFI) derived from the Canada Study of Health and Aging, the Rockwood Frailty Score (RFS), and the International Association of Nutrition and Aging 5-item a frailty scale (FS). Predictive models, using both unadjusted and adjusted logistic regressions, were created for each outcome. The unadjusted c-statistic was used to compare the predictive ability of each model.

RESULTS
A total of 341 patients were enrolled. Mean age was 76 ± 9 years, median Injury Severity Score was 13 [9–18], and median Glasgow Coma Scale score was 15 [12–15]. The unadjusted models indicated that both the TSFI and the RFS had comparable predictive value, as indicated by their unadjusted c-statistics, for mortality, in-hospital complications, skilled nursing facility disposition and 30-day readmission. Both TSFI and RFS models had unadjusted c-statistics indicating a relatively strong predictive ability for all outcomes. The unadjusted mFI and FS models did not have a strong predictive ability for predicting mortality and in-hospital complications. They also had a lower predictive ability for skilled nursing facility disposition and 30-day readmissions.

CONCLUSION
There are significant differences in the predictive ability of the four commonly used frailty scores. The TSFI and the RFS are better predictors of outcomes compared with the mFI and the FS. The TSFI is easy to calculate and might be used as a universal frailty score in geriatric trauma patients.

LEVEL OF EVIDENCE
Prognostic, level III.
Dose optimization of valproic acid in a lethal model of traumatic brain injury, hemorrhage, and multiple trauma in swine
Authors: Biesterveld Ben E. , Williams Aaron M. , Pai Manjunath P. , Dennahy Isabel S. , Graham Nathan J. , Chtraklin Kiril , Siddiqui Ali Z. , O'Connell Rachel L. , Bhatti Umar F. , Liu Baoling , Russo Rachel M. , Li Yongqing , Alam Hasan B. 
Published: August 2019

BACKGROUND
Trauma is a leading cause of death, and traumatic brain injury is one of the hallmark injuries of current military conflicts. Valproic acid (VPA) administration in high doses (300–400 mg/kg) improves survival in lethal trauma models, but effectiveness of lower doses on survival is unknown. This information is essential for properly designing the upcoming clinical trials. We, therefore, performed the current study to determine the lowest dose at which VPA administration improves survival in a model of lethal injuries.

METHODS
Swine were subjected to traumatic brain injury (10-mm cortical impact), 40% blood volume hemorrhage, and multiple trauma (femur fracture, rectus crush, and Grade V liver laceration). After 1 hour of shock, animals were randomized (n = 6/group) to four groups: normal saline (NS) resuscitation; or NS with VPA doses of 150 mg/kg (VPA 150) or 100 mg/kg (VPA 100) administered over 3 hours or 100 mg/kg over 2 hours (VPA 100 over 2 hours). Three hours after shock, packed red blood cells were given, and animals were monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test.

RESULTS
Without resuscitation, all of the injured animals died within 5 hours. Similar survival rates were observed in the NS (17%) and VPA 100 (0%) resuscitation groups. Survival rates in the 100-mg/kg VPA groups were significantly (p < 0.05) better when it was given over 2 hours (67%) compared to 3 hours (0%). 83% of the animals in the VPA 150 group survived, which was significantly higher than the NS and VPA 100 over 3 hours groups (p < 0.05).

CONCLUSION
A single dose of VPA (150 mg/kg) significantly improves survival in an otherwise lethal model of multiple injuries. This is a much lower dose than previously shown to have a survival benefit and matches the dose that is tolerated by healthy human subjects with minimal adverse effects.

LEVEL OF EVIDENCE
Therapeutic, level V.
The effect of cirrhosis on trauma outcomes: A systematic review and meta-analysis
Authors: Serrano Elina , Liu Pingyang , Nwabuo Adaobi I. , Langness Simone , Juillard Catherine 
Published: August 2019

BACKGROUND
The negative effect of cirrhosis on mortality following traumatic injury has been quantified in multiple observational studies. However, to our knowledge, the information contained in these studies has never been synthesized. The aims of this study were: (1) to determine the magnitude of the effect of liver cirrhosis on mortality, morbidity, and hospital course among trauma patients and (2) to analyze sources of study heterogeneity that may lead to differing estimates in the observed mortality rate among patients with cirrhosis.

METHODS
A systematic search of EMBASE and PubMed was conducted. Data were extracted from eligible studies and analyzed using a random-effects model to compare trauma outcomes in cirrhotic and noncirrhotic patients (PROSPERO Registration CRD42018088464). Mortality was the primary outcome. Secondary outcomes included complication rate, length of hospital stay, length of intensive care unit stay, and mechanical ventilation days.

RESULTS
Title and abstract review of 15,958 articles led to the identification of 31 relevant articles. Ultimately, 18 observational studies were included in this meta-analysis. The pooled effect sizes for mortality (odds ratio [OR], 4.52; 95% confidence interval [CI], 3.13–6.54) and complication rate (OR, 1.92; 95% CI, 1.30–2.85) were higher in the cirrhotic group than the noncirrhotic group. Trauma patients with cirrhosis also incurred longer hospital stays (mean difference, 3.81 days; 95% CI, 1.22–6.41) and longer ICU stays (mean difference, 2.40 days; 95% CI, 0.65–4.15). There was no difference in days spent on mechanical ventilation.

CONCLUSION
Preexisting liver cirrhosis is associated with increased mortality rate, complication rate, and length of hospitalization among trauma patients, even after adjusting for confounding factors and potential sources of between-study heterogeneity. Trauma patients with cirrhosis would benefit from heightened surveillance and injury prevention interventions.

LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Role of resveratrol in protecting vasodilatation function in septic shock rats and its mechanism
Authors: Zhang Zi-sen , Zhao Hong-liang , Yang Guang-ming , Zang Jia-tao , Zheng Dan-yang , Duan Chen-yang , kuang Lei , Zhu Yu , Wu Yue , Li Tao , Liu Liang-ming 
Published: August 2019

BACKGROUND
Vascular dysfunction is a major cause of sepsis-induced multiple-organ dysfunction. Resveratrol is a polyphenol compound with extensive pharmacological effects including anti-inflammation. The aim of this study was to determine the role and mechanism of resveratrol in protecting vascular function following sepsis.

METHODS
The cecal ligation and puncture method was used to establish a septic shock rat model. Resveratrol (5 mg/kg and 10 mg/kg) was administered intravenously immediately and at 12 hours after cecal ligation and puncture, respectively. The effects of resveratrol on vasodilatation function, blood flow velocity, hemodynamics, and vital organ function and its relationship to Rac-1 and HIF-1α were observed.

RESULTS
Vascular relaxation reactivity and blood flow velocity were significantly decreased after septic shock, both were significantly improved by resveratrol 5 mg/kg and 10 mg/kg, and the effect of 10 mg/kg was greater. The relaxation reactivity of the superior mesenteric artery to acetylcholine (Ach) was increased by 43.2%. The blood flow velocity of mesenteric arterioles and venules was increased by 47.1% and 51%, respectively, after resveratrol (10 mg/kg) administration compared with the septic shock group. The hemodynamics and both liver and kidney blood flow were significantly decreased after septic shock, which were significantly improved them by resveratrol, which enhanced the vascular relaxation reactivity in septic shock rats. The 72-hour survival rate of septic shock rats in the resveratrol group (62.5%) was significantly higher than that in the septic shock group (6.3%). Resveratrol significantly upregulated the expression of endothelial nitric oxide synthase (eNOS) and downregulated the expression of inducible NOS, Rac-1, and HIF-1α. Inhibitors of Rac-1 and HIF-1α significantly improved the expression of eNOS, and inhibition of eNOS (L-NAME, 5 mg/kg) antagonized the resveratrol-induced improvement in vascular relaxation reactivity and survival.

CONCLUSION
Resveratrol was beneficial for vasodilatation function in rats with septic shock, which is the major contribution to resveratrol improving hemodynamics and organ perfusion. The mechanism involved resveratrol upregulating the expression of eNOS by inhibiting Rac-1 and HIF-1α.