bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of Tenofovir Alafenamide in People With HIV Who Experienced Proximal Renal Tubulopathy on Tenofovir Disoproxil Fumarate
Authors: Campbell Lucy , Barbini Birgit , Burling Keith , Cromarty Ben , Hamzah Lisa , Johnson Margaret , Jones Rachael , Samarawickrama Amanda , Williams Deborah , Winston Alan , Post Frank A. ,   FANTA trial team
Published: June 2021

Background:
Proximal renal tubulopathy (PRT) is an infrequent complication of tenofovir disoproxil fumarate (TDF). It remains to be established whether tenofovir alafenamide (TAF) can be safely administered to individuals who experienced PRT on TDF.

Methods:
Individuals with a history of TDF-associated PRT and current estimated glomerular filtration rate (eGFR) over 30 mL/min/1.73 m2 initiated TAF and were followed for 96 weeks. The primary outcome of interest was recurrent PRT. Secondary outcomes were changes in kidney biomarkers, bone biomarkers, and bone mineral density (BMD). Data were analyzed using multilevel mixed-effects linear regression models. The trial was registered under EudraCT 2016-003345-29.

Results:
All 31 participants [median age 55 (inter-quartile range 51, 60) years, 97% men, 87% White ethnicity] remained on TAF at week 96, and none developed glycosuria or recurrent PRT. Participants experienced small declines in eGFR-creatinine [−1.9 (95% confidence interval: −3.5 to −0.3) mL/min/1.73 m2/yr; P = 0.024], but not in eGFR-cystatin C [−0.9 (−2.1 to 0.4) mL/min/1.73 m2/yr; P = 0.16]. Ten (32%) and 5 (16%) participants experienced rapid (>5 mL/min/1.73 m2/yr) decline in eGFR-creatinine and eGFR-cystatin C. No significant change in other kidney biomarkers, bone turnover, or BMD was observed (P > 0.2).

Conclusions:
In individuals with a history of PRT on TDF, 96 weeks of TAF was not associated with recurrent PRT or adverse effects on renal tubular function, bone turnover, or BMD. These data suggest that TAF is a treatment option for this vulnerable population.
HIV-1 Nucleic Acids Identify Rectal HIV Exposures in Self-Collected Rectal Swabs, Whereas Y-Chromosome Single Tandem Repeat Mixtures Are Not Reliable Biomarkers of Condomless Receptive Anal Intercourse
Authors: Lemos Maria P. , Nandi Vijay , Dragavon Joan , Fleming Ira , Krishnan Keertana , Musuruana Martin , Kramer Madeline , Glantz Hayley , Andrasik Michele , Coombs Robert W. , McElrath M. Juliana , Tieu Hong-Van 
Published: June 2021

Background:
To focus interventions, biomarkers of HIV-1 exposure could help in identifying subpopulations at highest risk of acquisition. We assessed whether Y-chromosome single tandem repeat (YSTR) mixtures obtained from rectal swabs could serve as a biomarker of condomless receptive anal intercourse (CRAI) among men who have sex with men and transgender women and evaluated the feasibility of detecting HIV-1 virions to assess exposures.

Methods:
Twenty-nine sexually active HIV-seronegative men who have sex with men and one transgender woman from New York City answered on-site and mobile app sexual behavior questionnaires. They were randomized to collecting self-administered rectal swabs every morning or after receptive anal intercourse (RAI). YSTR profiles were assessed from blood sample and swabs; HIV-1 exposure was measured by conducting quantitative polymerase chain reaction in swabs.

Results:
After 2 months, the daily mobile survey had 135%–201% more instances of anal sex acts and 170%–193% more RAI than on-site surveys. Daily mobile reporting had 11%–35% less CRAI events than those reported on-site (P
daily = 0.001; P
per-sex = 0.047). The daily swabbing arm reported less RAI (P < 0.001) and CRAI (P < 0.038) and had 2.95 lower odds of detecting YSTR mixtures (P = 0.021) than the per-sex-event arm. Surprisingly, YSTR detection was not significantly modified by report of bowel movements and lubricant, enema, or condom use. No participant became HIV-1 infected, yet HIV-1 total nucleic acids were detected in 6 independent episodes of CRAI in 2 participants taking pre-exposure prophylaxis.

Conclusions:
YSTR mixtures demonstrated 80% specificity but only 30% sensitivity as a biomarker of CRAI in self-collected rectal swabs. However, detection of HIV-1 exposures in self-collected swabs may help in identifying those needing further HIV risk reduction strategies.
Quality and Safety in Healthcare, Part LXXXIX
Authors: Harolds Jay A. 
Published: June 2021

Abstract
A major priority of the Toyota Production System is to satisfy the customers by providing high value. The use of continuous flow, pull systems, the Andon system, standard work, visual controls, the 5S system, and reliable technology are critically important. Optimizing one’s workforce is also very important by developing leaders and teams, using consensus in decision making, and becoming a learning organization. To fully understand the problems, it is also important that leaders go to the workplace to talk to workers and see what is going on.
Reliability of Quantitative 18F-FDG PET/CT Imaging Biomarkers for Classifying Early Response to Chemoradiotherapy in Patients With Locally Advanced Non–Small Cell Lung Cancer
Authors: Horn Kevin P. , Thomas Hannah M.T. , Vesselle Hubert J. , Kinahan Paul E. , Miyaoka Robert S. , Rengan Ramesh , Zeng Jing , Bowen Stephen R. 
Published: June 2021

Purpose of the Report
We evaluated the reliability of 18F-FDG PET imaging biomarkers to classify early response status across observers, scanners, and reconstruction algorithms in support of biologically adaptive radiation therapy for locally advanced non–small cell lung cancer.

Patients and Methods
Thirty-one patients with unresectable locally advanced non–small cell lung cancer were prospectively enrolled on a phase 2 trial (NCT02773238) and underwent 18F-FDG PET on GE Discovery STE (DSTE) or GE Discovery MI (DMI) PET/CT systems at baseline and during the third week external beam radiation therapy regimens. All PET scans were reconstructed using OSEM; GE-DMI scans were also reconstructed with BSREM-TOF (block sequential regularized expectation maximization reconstruction algorithm incorporating time of flight). Primary tumors were contoured by 3 observers using semiautomatic gradient-based segmentation. SUVmax, SUVmean, SUVpeak, MTV (metabolic tumor volume), and total lesion glycolysis were correlated with midtherapy multidisciplinary clinical response assessment. Dice similarity of contours and response classification areas under the curve were evaluated across observers, scanners, and reconstruction algorithms. LASSO logistic regression models were trained on DSTE PET patient data and independently tested on DMI PET patient data.

Results
Interobserver variability of PET contours was low for both OSEM and BSREM-TOF reconstructions; intraobserver variability between reconstructions was slightly higher. ΔSUVpeak was the most robust response predictor across observers and image reconstructions. LASSO models consistently selected ΔSUVpeak and ΔMTV as response predictors. Response classification models achieved high cross-validated performance on the DSTE cohort and more variable testing performance on the DMI cohort.

Conclusions
The variability FDG PET lesion contours and imaging biomarkers was relatively low across observers, scanners, and reconstructions. Objective midtreatment PET response assessment may lead to improved precision of biologically adaptive radiation therapy.
Characterizing Concomitant Follicular Lymphoma and Gastric Carcinoma Using 68Ga-FAPI-04 and 18F-FDG PET/CT
Authors: Chen Xuetao , Wei Maomao , Wang Shuailiang , Yang Zhi , Wang Xuejuan 
Published: June 2021

Abstract
We herein report a case involving a 67-year-old man with concomitant progressive follicular lymphoma and gastric carcinoma. Baseline 18F-FDG PET/CT showed high metabolic activity in multiple nodal stations and a thickened gastric antrum wall, whereas 68Ga-FAPI-04 PET/CT depicted very intense tracer uptake in the gastric lesion but mild uptake in the nodes. After the treatment, complete remission from lymphadenopathy was achieved, whereas the gastric lesion accumulated more radiotracers compared with baseline levels. Despite our incorrect initial assumption of B-cell transformation, molecular imaging was able to profile the characteristics of these 2 diseases.
Two-Stage Treatment of a Large Premaxillary Defect
Authors: Dibbs Rami P. , Beh Han Zhuang , Ferry Andrew M. , Davies Lesley W. , Nguyen Jenny L. , Reece Edward M. , Alfi David M. , Pederson William C. , Buchanan Edward P. 
Published: June 2021

Abstract
Bilateral cleft lip and palate (CLP) patients commonly require surgical management to treat maxillary hypoplasia following the primary repair. Rarer is the CLP patient who also presents with a missing premaxillary segment. Here the authors present the case of a 19-year-old female with a history of bilateral CLP who demonstrated significant maxillary hypoplasia in addition to a large premaxillary defect. To correct this deformity, LeFort I advancement with fibular reconstruction of the maxilla and dental implant placement was performed as a single surgical procedure. The authors discuss the advantages of undergoing this single-staged operation. By utilizing virtual surgical planning (VSP) and incorporating a multidisciplinary team within the operating room, the patient was able to successfully undergo maxillary reconstruction and dental implant placement in a single operation.
Craniosynostosis of the Metopic Suture in a Patient With CADASIL/Lehman Syndrome
Authors: Riordan Coleman P. , Lyon Helen N. , McIntyre Joyce K. 
Published: June 2021

Abstract
A 3-month-old patient presented for evaluation by plastic surgery with marked trigonocephaly and was subsequently diagnosed with metopic craniosynostosis. During presurgical evaluation, the patient was found to have two variants of the NOTCH3 gene, resulting in the diagnosis of lateral meningocele (Lehman) syndrome. Due to the increased possibility of stroke associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the patient underwent only anterior calvarial vault remodeling without fronto-orbital advancement for correction of her craniosynostosis. This unique constellation of symptoms, and its impact on operative management, has not been previously described in the literature.
One Triangle-Blepharoplasty Flap for Anterior Lamellae Pretarsal Defects on the Upper Eyelid
Authors: Díez-Montero Cecilia , Marqués-Fernández Victoria E. , Galindo-Ferreiro Alicia 
Published: June 2021

Purpose:The aim of this study is to present the outcomes of one triangle blepharoplasty flap upper eyelid (UE) reconstruction. It is a hardly recognized technique used to repair anterior lamella pretarsal defects resulting from the removal of lesions on the UE.Methods:Retrospective review of three excised lesions reconstructed with one triangle-blepharoplasty flap technique between 2017 and 2020 at Río Hortega University Hospital in Valladolid, Spain. It is a technique to reconstruct wide-based anterior lamella UE lesions, 25% to 50% UE length. Demographic characteristics, histology results and complications are presented.Results:Medical records of three patients have been reviewed with a minimum follow-up of 6 months (mean follow up of 16 months). The patient's average age was 67 years. Histology results were three seborrheic keratosis. There were no intra or post-surgical complications and all had good functional and aesthetic upper lid results.Conclusions:The reconstruction of pretarsal lesions limited to the anterior lamella of the UE using one triangle-blepharoplasty flap is a technique with good functional and aesthetic results.
Facial Contouring Surgery Using Facelift Approach
Authors: Lee Yoon Joo , Lee Cho Long , Lee Il Seok , Yang Ho Jik 
Published: June 2021

Background:
In Asian women who undergo facelift surgery, satisfying results are achieved for facial rhytides, but there have been complaints concerning malar prominence and mandible angle region postoperatively. Anatomically, compared with the Caucasians, the Asians have a thick skin and a wide and short facial geometry. The Asians generally have a protruded zygoma and prominent mandible angles; accordingly, their bony contouring surgery that is the base frame in facelift must be considered. The authors aimed to investigate the effects of performing facial contouring surgery and facelift simultaneously to achieve oval facial contour and youthful face.

Methods:
The authors assessed 21 Asian women who simultaneously underwent facial contouring surgery with facelift between March 2014 and March 2018. The clinical results were assessed based on preoperative and postoperative photographs and the global aesthetic improvement scale score.

Results:
Surgery was successful in all patients. Postoperatively, improvements in facial rhytides and appropriate facial contour were achieved. All patients were satisfied with the outcomes. Some patients experienced short-term complication; however, these complications improved. Serious long-term complications were not noted.

Conclusions:
Highly satisfying outcomes can be achieved with combined facial contouring surgery and facelift for Asian women with a wide face.
The Role of Facial Expression Analysis and Electrodermal Activity as an Objective Evaluation of Persistent Idiopathic Facial Pain
Authors: Rokicki Jan Pavel , Ivanauskas Andrius , Janužis Gintaras 
Published: June 2021

Abstract
Persistent idiopathic facial pain (PIFP) is an enigmatic condition presenting with variable features. Psychiatric comorbidities are speculated to influence PIFP.
In this study, the authors evaluated patients with PIFP through the hospital anxiety and depression scale, facial expression analysis, and electrodermal activity.
A total of 67 respondents enrolled as the experimental group and 28 participants as the control group. Pain scores were higher in the experimental group (5.24; SD 2.349) P < 0.001 depression (5.58 (SD 3.766) versus 3.07 (SD 2.418), P = 0.002) and anxiety scores (9.78 (SD 4.923) versus 6.75 (SD 4.097) P = 0.007) were higher in the experimental group. The experimental group expressed more negative episodes (P = 0.024); Electrodermal Activity data in terms of peaks/min (P = 0.872) and average peak amplitude (P = 0.168) were not significantly different between the groups.
It may be concluded that pain levels may be influenced by psychiatric comorbidity as PIFP patients showed insignificant physiological response to pain.
Exploration of the Function of Ginsenoside RD Attenuates Lipopolysaccharide-Induced Lung Injury: A Study of Network Pharmacology and Experimental Validation
Authors: Yang Bo , Wang Rong , Ji Lin-Lin , Li Xiao-Ping , Li Xiao-He , Zhou Hong-Gang , He Zhan-Kun , Xu Hong-Liang , Meng Fan-Jie , Wang Guang-Shun 
Published: June 2021

ABSTRACT

Objective:
Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms.

Methods:
GSRd-target-ALI–related gene set was constructed. And bioinformatics tools were used to discover the potential mechanism. We observed the survival of subjects for 72 h. In addition, male BALB/c mice were intraperitoneal injected with GSRd (25 and 50 mg/kg) after received one intratracheal instillation of LPS. Inflammatory changes, oxidative stress, and phosphorylation were assessed to study the biological effects.

Results:
A total of 245 interaction genes were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were enriched in immune-inflammatory system. Among them, PI3K-Akt signaling pathway was the highest-ranked pathway of inflammatory response. In vivo study, it was found that GSRd improved survival in endotoxemic mice and inhibited the major characteristic of ALI. And the p-PI3K and p-Akt expression was significantly decreased by GSRd treatment.

Conclusion:
GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.
Pathomechanisms Underlying Hypoxemia in Two COVID-19-Associated Acute Respiratory Distress Syndrome Phenotypes: Insights From Thrombosis and Hemostasis
Authors: Gando Satoshi , Wada Takeshi 
Published: June 2021

ABSTRACT

Background:
The pathomechanisms of hypoxemia and treatment strategies for type H and type L acute respiratory distress syndrome (ARDS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) have not been elucidated.

Main text:
SARS-CoV-2 mainly targets the lungs and blood, leading to ARDS, and systemic thrombosis or bleeding. Angiotensin II-induced coagulopathy, SARS-CoV-2-induced hyperfibrin(ogen)olysis, and pulmonary and/or disseminated intravascular coagulation due to immunothrombosis contribute to COVID-19-associated coagulopathy. Type H ARDS is associated with hypoxemia due to diffuse alveolar damage-induced high right-to-left shunts. Immunothrombosis occurs at the site of infection due to innate immune inflammatory and coagulofibrinolytic responses to SARS-CoV-2, resulting in microvascular occlusion with hypoperfusion of the lungs. Lung immunothrombosis in type L ARDS results from neutrophil extracellular traps containing platelets and fibrin in the lung microvasculature, leading to hypoxemia due to impaired blood flow and a high ventilation/perfusion (VA/Q) ratio. COVID-19-associated ARDS is more vascular centric than the other types of ARDS. D-dimer levels have been monitored for the progression of microvascular thrombosis in COVID-19 patients. Early anticoagulation therapy in critical patients with high D-dimer levels may improve prognosis, including the prevention and/or alleviation of ARDS.

Conclusions:
Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients.
Wearable Patch Heart Rate Variability Is an Early Marker of Systemic Inflammation During Experimental Human Endotoxemia
Authors: Koeneman Mats , Koch Rebecca , van Goor Harry , Pickkers Peter , Kox Matthijs , Bredie Sebastian 
Published: June 2021

ABSTRACT

Introduction:
Early diagnosis and treatment can reduce the risk of organ failure and mortality in systemic inflammatory conditions. Heart rate variability (HRV) has potential for early identification of the onset of systemic inflammation, as it may detect changes in sympathetic nervous system activity resulting from the developing inflammatory response before clinical signs appear. With the use of new methodologies, we investigated the onset and kinetics of HRV changes as well as several inflammatory parameters and symptoms during experimental human endotoxemia, a model of systemic inflammation in humans in vivo.

Patients and Methods:
Healthy volunteers were intravenously administered LPS (n = 15) or placebo (n = 15). HRV was determined using a wireless wearable device, and parameters low to high frequency (LF:HF) ratio, root mean square of the successive differences (RMSSD), and standard deviation of normal-to-normal R-R intervals (SDNN)were calculated through 1-min-rolling 6-min windows. Plasma cytokine levels and flu-like symptoms and vital signs were serially assessed.

Results:
The increase in LF:HF ratio, reflecting sympathetic predominance, was more pronounced in the LPS group compared to the placebo group, with the difference becoming statistically significant 65 min following LPS administration (1.63 [1.42–1.83] vs. 1.28 [1.11–1.44], P = 0.005). Significant between-group differences in RMSSD and SDNN were observed from 127 to 140 min post-LPS administration onwards, respectively. Plasma cytokine levels showed significant between-group differences staring 60 min post-LPS. For symptom score, heart rate, temperature, and diastolic blood pressure, significant differences compared with the placebo group were observed at 90, 118, 120, and 124 min post-LPS, respectively.

Conclusion:
In a controlled human model of systemic inflammation, elevations in the LF:HF ratio followed very shortly after elevations in plasma cytokine levels and preceded onset of flu-like symptoms and alterations in vital signs. HRV may represent a promising non-invasive tool for early detection of a developing systemic inflammatory response.
Effects of Sodium Thiosulfate During Resuscitation From Trauma-and-Hemorrhage in Cystathionine Gamma Lyase (CSE) Knockout Mice
Authors: Gröger Michael , Hogg Melanie , Abdelsalam Essam , Kress Sandra , Hoffmann Andrea , Stahl Bettina , Saub Veronique , Denoix Nicole , McCook Oscar , Calzia Enrico , Wolfschmitt Eva-Maria , Wachter Ulrich , Vogt Josef A. , Wang Rui , Radermacher Peter , Merz Tamara , Nussbaum Benedikt L. 
Published: June 2021

ABSTRACT

Background:
Sodium thiosulfate (Na2S2O3) is a clinically established drug with antioxidant and sulphide-releasing properties. Na2S2O3 mediated neuro- and cardioprotective effects in ischemia/reperfusion models and anti-inflammatory effects in LPS-induced acute lung injury. Moreover, Na2S2O3 improved lung function during resuscitation from hemorrhagic shock in swine with pre-existing atherosclerosis, characterized by decreased expression of cystathionine γ-lyase (CSE), a major source of hydrogen sulfide (H2S) synthesis in the vasculature. Based on these findings, we investigated the effects of Na2S2O3 administration during resuscitation from trauma-and-hemorrhage in mice under conditions of whole body CSE deficit.

Methods:
After blast wave-induced blunt chest trauma and surgical instrumentation, CSE knockout (CSE−/−) mice underwent 1 h of hemorrhagic shock (MAP 35 ± 5 mm Hg). At the beginning of resuscitation comprising retransfusion, norepinephrine support and lung-protective mechanical ventilation, animals received either i.v. Na2S2O3 (0.45 mg g−1, n = 12) or vehicle (saline, n = 13). Hemodynamics, acid–base status, metabolism using stable isotopes, and visceral organ function were assessed. Blood and organs were collected for analysis of cytokines, mitochondrial respiratory capacity, and immunoblotting.

Results:
Na2S2O3 treatment improved arterial paO2 (P = 0.03) coinciding with higher lung tissue glucocorticoid receptor expression. Norepinephrine requirements were lower in the Na2S2O3 group (P < 0.05), which was associated with lower endogenous glucose production and higher urine output. Na2S2O3 significantly increased renal tissue IκBα and heme oxygenase-1 expression, whereas it lowered kidney IL-6 and MCP-1 levels.

Conclusion:
Na2S2O3 exerted beneficial effects during resuscitation of murine trauma-and-hemorrhage in CSE−/− mice, confirming and extending the previously described organ-protective and anti-inflammatory properties of Na2S2O3. The findings make Na2S2O3 a potentially promising therapeutic option in the context of impaired CSE activity and/or reduced endogenous H2S availability.
Juxtapapillary Choroidal Neovascular Membrane as a Complication of Optic Disc Drusen: Multimodal Imaging With Swept Source-Optical Coherence Tomography and Optical Coherence Tomography Angiography
Authors: Douglas Vivian Paraskevi , Douglas Konstantinos A. A. , Miller John B. , Cestari Dean M. 
Published: June 2021

Abstract:
A 55-year-old Caucasian man presented to the neuro-ophthalmology department for follow-up evaluation due to long-standing bilateral optic nerve head drusen (ONHD). On examination, the BCVA was 20/20-2 in both eyes. Dilated fundus examination revealed extensive ONHD in both eyes, retinal hemorrhages, exudates inferonasal to the macula, and macular edema inferotemporal to the disc margin. Automated visual field testing revealed generalized depression in both eyes. Late phase leakage was observed on fluorescein angiography (FA). Optical coherence tomography angiography identified a small juxtapapillary choroidal neovascular membrane inferonasal to the macula in the right eye correlating with the area of retinal hemorrhage and exudates.