bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of islatravir in HIV treatment and prevention: an update
Authors: Derbalah Abdallah , Karpick Hayley Christine , Maize Holly , Skersick Preston , Cottrell Mackenzie , Rao Gauri G. 
Published: June 2022

Purpose of review
To summarize recent updates on the potential role of islatravir for HIV treatment and prevention.

Recent findings
Islatravir is an investigational antiretroviral agent with unique pharmacologic properties that facilitate flexible dosing regimens. Islatravir has demonstrated potent antiviral activity and a high barrier to resistance when combined with doravirine and lamivudine. A simplified two-drug HIV treatment regimen of islatravir combined with doravirine has also demonstrated comparable efficacy to standard of care three-drug regimens. The long half-life and high potency of islatravir's active metabolite may support its use as a long-acting option for HIV preexposure prophylaxis (PrEP). A once monthly oral dose of islatravir maintains effective concentrations of its active metabolite over the entire dosing interval. Furthermore, an investigational implantable formulation has been projected to provide efficacious concentrations for at least a year and exhibits comparable distribution into vaginal and rectal tissues making it a promising PrEP option for male and female individuals. Islatravir has minimal risks of drug interactions as it is not a substrate, inducer, or inhibitor of major drug metabolizers and transporters. Finally, clinical trials demonstrate islatravir's favorable safety profile revealing only mild and transient adverse events.

Summary
Leveraging the unique pharmacological properties of islatravir offers opportunities for simplified HIV treatment regimens and long-acting PrEP making it a valuable addition to the antiretroviral arsenal.
Sirtuin1 inhibitor attenuates hypertension in spontaneously hypertensive rats: role of Giα proteins and nitroxidative stress
Authors: Arifen Nahida , Li Yuan , Srivastava Ashok K. , Anand-Srivastava Madhu B. 
Published: June 2022

Background:
We recently showed that vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) exhibit overexpression of Sirtuin1 (Sirt1) that contributes to the enhanced expression of Giα proteins implicated in the development of hypertension in SHR.

Method:
The present study investigated if the inhibition of Sirt1 could also ameliorate hypertension in SHR and explore the underlying molecular mechanisms. For this study, a selective inhibitor of Sirt1, EX-527 (5 mg/kg of body weight), was injected intraperitoneally into 8-week-old SHR and age-matched Wistar Kyoto (WKY) rats twice per week for 3 weeks. The blood pressure (BP) and heart rate was measured twice a week by the CODA noninvasive tail cuff method.

Results:
The high BP and augmented heart rate in SHR was significantly attenuated by EX-527 treatment, which was associated with the suppression of the overexpression of Sirt1 and Giα proteins in heart, VSMC and aorta. In addition, the enhanced levels of superoxide anion, NADPH oxidase activity, overexpression of NADPH oxidase subunits and FOXO1 were attenuated and the decreased levels of endothelial nitric oxide synthase (eNOS), nitric oxide and increased levels of peroxynitrite (ONOO-) and tyrosine nitration in VSMC from SHR were restored to control levels by EX-527 treatment. Furthermore, knockdown of FOXO1 by siRNA also attenuated the overexpression of Giα-2 and NADPH oxidase subunit proteins and restored the decreased expression of eNOS in VSMC from SHR.

Conclusion:
These results suggest that the inhibition of overexpressed Sirt1 and its target FOXO1 through decreasing the enhanced levels of Giα proteins and nitro-oxidative stress attenuates the high BP in SHR.
Association of home and office systolic and diastolic hypertension with glucose metabolism in a general population: the Ohasama study
Authors: Tatsumi Yukako , Satoh Michihiro , Asayama Kei , Murakami Takahisa , Hirose Takuo , Hara Azusa , Tsubota-Utsugi Megumi , Inoue Ryusuke , Kikuya Masahiro , Nomura Kyoko , Metoki Hirohito , Hozawa Atsushi , Katagiri Hideki , Imai Yutaka , Ohkubo Takayoshi 
Published: June 2022

Objective:
This study was performed to investigate the association of hypertension subtypes with glucose metabolism among the Japanese general population.

Methods:
The study involved 646 residents (mean age: 62.4 years) without treatment for hypertension or a history of diabetes from Ohasama, a rural Japanese community, who underwent an oral glucose tolerance test. Hypertension subtypes [normotension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic and diastolic hypertension (SDH)] were defined on the basis of home and office SBP and DBP (HBP and OBP, respectively). The estimated means of blood glucose related indices among the groups were compared by analysis of covariance adjusted for possible confounding factors.

Results:
Blood glucose related indices were not different among the morning HBP-defined hypertension subtypes. Participants with evening HBP-defined ISH had a significantly higher estimated mean BG at 120 min, higher homeostasis model assessment-insulin resistance (HOMA-IR) and lower Matsuda–DeFronzo index than participants with NT (all P < 0.021). Participants with OBP-defined SDH had a significantly higher estimated mean fasting blood glucose; blood glucose at 30, 60 and 120 min; and HOMA-IR and a lower Matsuda–DeFronzo index than participants with NT (all P < 0.0025).

Conclusion:
The blood glucose related indices were different among hypertension subtypes. Participants with evening HBP-defined ISH and OBP-defined SDH had higher blood glucose levels and insulin resistance than participants with correspondingly defined normotension, while those with morning HBP did not. These findings suggest the importance of measuring evening HBP and office blood pressure for early detection of coexisting hypertension and diabetes.
Spot urinary sodium to monitor relative changes in population salt intake during the UK salt reduction programme
Authors: Tan Monique , Wang Changqiong , Song Jing , He Feng J. , MacGregor Graham A. 
Published: June 2022

Objectives:
The most accurate method to measure population salt intake is to collect the complete 24-h urinary sodium excretion (24-h UNa) but it is resource intensive and is rarely carried out frequently. We, therefore, assessed the use of spot urinary sodium concentration to monitor relative changes in population salt intake in between 24-h urine surveys.

Methods:
We used 24-h (n = 2020) and spot urine (n = 21 711) samples drawn from adult participants in separate, cross-sectional, nationally representative surveys in England, repeated between 2006 and 2014.

Results:
As population average 24-h UNa fell from 2006 to 2014 (from 8.7 to 7.6 g/day, i.e. by 12%) with the ongoing salt reduction programme, spot sodium concentration fell by a similar extent (from 106.1 to 93.1 mmol/l, i.e. by 13%). The regression slopes of 24-h UNa and spot sodium concentration ran parallel (P value = 0.1009) in a linear regression modelling the difference in their year-on-year changes [by regressing the 24-h UNa or sodium concentration values on time, estimation method (24-h versus spot), and their interaction term]. In contrast, when 24-h UNa was estimated by applying the Kawasaki, Tanaka, or INTERSALT formulas to spot sodium concentrations, almost no change was detected from 2006 to 2014 (±1%) and their regression slopes were significantly different from that of the measured 24-h UNa (all P values <0.0001).

Conclusion:
Spot urinary sodium concentration drawn from random and representative samples of the population accurately reflected relative changes in population average 24-h UNa, and can therefore, be used in between 24-h urine surveys to monitor population salt reduction programmes. Formulas commonly used to estimate 24-h UNa were unsuitable to do so.
Role of the angiotensin type 1 receptor in modulating the carotid chemoreflex in an ovine model of renovascular hypertension
Authors: Sohn Chris Sung-Eun , Chang Joshua Wen-Han , George Bindu , Chen Siyi , Ramchandra Rohit 
Published: June 2022

Objective:
The carotid body has been implicated as an important mediator and putative target for hypertension. Previous studies have indicated an important role for angiotensin II in mediating carotid body function via angiotensin type-1 receptors (AT1R); however, their role in modulating carotid body function during hypertension is unclear.

Methods:
Using a large preclinical ovine model of renovascular hypertension, we hypothesized that acute AT1R blockade would lower blood pressure and decrease carotid body-mediated increases in arterial pressure. Adult ewes underwent either unilateral renal artery clipping or sham surgery. Two weeks later, flow probes were placed around the contralateral renal and common carotid arteries.

Results:
In both hypertensive and sham animals, carotid body stimulation using potassium cyanide caused dose-dependent increases in mean arterial pressure but a reduction in renal vascular conductance. These responses were not different between groups. Infusion of angiotensin II led to an increase in arterial pressure and reduction in renal blood flow. The sensitivity of the renal vasculature to angiotensin II was significantly attenuated in hypertension compared with the sham animals. Systemic inhibition of the AT1R did not alter blood pressure in either group. Interestingly carotid body-evoked arterial pressure responses were attenuated by AT1R blockade in renovascular hypertension but not in shams.

Conclusion:
Taken together, our findings indicate a decrease in vascular reactivity of the non-clipped kidney to angiotensin II in hypertension. The CB-evoked increase in blood pressure in hypertension is mediated in part, by the AT1R. These findings indicate a differential role of the AT1R in the carotid body versus the renal vasculature.
Overlapping Signs and Symptoms Between Recurrent Varicella and Pityriasis rosea Gibert
Authors: Baba Koichi , Baba Tomoko , Ogra Pearay L. , Okuno Toshiomi 
Published: June 2022

Background:
Pityriasis rosea Gibert (PRG) has features similar to those of common infectious childhood diseases, suggesting a viral cause, but no agent has been identified to date. We describe 4 children with PRG and 2 with recurrent varicella who were studied using photochronography, virology and immunology.

Methods:
The 6 patients with skin rashes visited our pediatric clinic from April 2012 to May 2016. Photographs of their skin lesions were taken; blood, skin lesions, and/or nasal lavage samples were collected to detect varicella-zoster virus (VZV) DNA and antibodies; and skin tests were carried out to measure cell-mediated immunity to VZV.

Results:
Herald patches were confirmed in 2 of 4 PRG patients. No specimen cultures were positive for infectious VZV. However, VZV-DNA was detected in skin lesions of 3 PRG patients. During the acute phase, 5 patients had IgG antibodies to VZV, and skin-test reactions were positive in 5 patients.

Conclusions:
IgG antibody titers to VZV at rash onset were high, suggesting that they were already rising at the appearance of the rash and that reinfection with VZV must have occurred during the prodromal stage or several weeks before rash appearance in PRG patients whose immunity had declined below the threshold. Our study suggests a new pathogenesis of PRG that might help to address incongruities of past theories on PRG sites of viral entry and replication, incubation period and variations in the clinical course of PRG from prodrome to healing.
Timing of Monovalent Vaccine Administration in Infants Receiving DTaP-based Combination Vaccines in the United States
Authors: Marshall Gary S. , Petigara Tanaz , Liu Zhiwen , Wolfson Lara , Johnson David , Goveia Michelle G. , Chen Ya-Ting 
Published: June 2022

Background:
The recommended US infant immunization schedule includes doses of diphtheria, tetanus, acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) and hepatitis B virus (HepB) during the first 6 months of life. Little information is available about the timing of associated, complementary monovalent vaccine administration in infants receiving DTaP-based pentavalent combination vaccines.

Methods:
This was a retrospective cohort study of infants born between July 1, 2010, and June 30, 2018, in the US MarketScan commercial claims and encounters database. Descriptive statistics were used to assess vaccine administration patterns. Multivariate logistic regression was performed to explore factors associated with coadministration of DTaP-IPV/Hib and HepB.

Results:
Among infants who received DTaP-HepB-IPV (n = 129,885), 93.7% had claims for at least 2 Hib doses; most (91.5%‐98.3%) of these doses were administered on the same day as DTaP-HepB-IPV doses. Among infants who received DTaP-IPV/Hib (n=214,172), 95.3% had claims for ≥2 doses of HepB. Although coverage was high, 59.2% received the second HepB dose on the same day as the first DTaP-IPV/Hib dose, and 44.6% received the third dose of HepB on the same day as the third DTaP-IPV/Hib dose. Differences in coadministration of the second and third HepB doses with DTaP-IPV/Hib were associated with the region of residence, provider type, health plan type and coadministration of pneumococcal conjugate vaccine and rotavirus vaccine.

Conclusions:
Almost all infants received the appropriate, complementary monovalent vaccine series. However, this study found variability in the timing of HepB doses in relation to DTaP-IPV/Hib doses with many infants not completing the HepB series until 9 months of age.
Extended Work Shifts Increase Subjective Pain Complaints Among Cabin Crewmembers, but Not Among Airline Pilots or Healthcare Workers
Authors: Matre Dagfinn , Goffeng Elisabeth , Nordby Karl-Christian , Lie Jenny-Anne S. 
Published: June 2022

ObjectiveTo determine whether four consecutive extended work shifts are associated with an increased risk of subjective pain complaints, sleep duration, and sleep disturbances.MethodsForty-three healthcare workers, 41 cabin crewmembers, and 18 airline pilots working 4 consecutive extended workdays reported subjective pain complaints and sleep after the 1st and 4th workday.ResultsThe risk of headache (odds ratio [OR] 21.4, 95% confidence interval [CI] 1.85 to 246.5) and pain in the hands, arms, or wrists (OR 3.78, 95% CI 1.84 to 7.76) increased after workday 4 versus workday 1 in cabin crewmembers. Sleep duration was longer (0.6 to 1.1 hours), and sleep disturbances fewer, the night before the fourth extended workday, compared with before the first workday, in all occupations.ConclusionsWe found no general support for an association between extended work shifts and subjective pain, whereas sleep duration was improved, and sleep disturbances reduced after 4 consecutive extended workdays.
Giant Cholesteatoma: A Case Report and Review of the Literature
Authors: Wong Wai Keat , Lee Michael Fook-Ho , Saxby Alexander J. 
Published: June 2022

Objective
To present a case of giant cholesteatoma and review of the contemporary literature.

Patients
A 61-year-old male presented with foul-smelling discharge from his right ear in the setting of a previous canal wall down mastoidectomy. Otomicroscopy demonstrated a mastoid cavity filled with infected keratinous debris. Neuro-imaging revealed soft tissue inflammatory changes in the mastoid cavity, with involvement of the temporomandibular joint (TMJ) and parotid gland and tegmen erosion. Biopsies showed evidence of desquamated epithelium consistent with cholesteatoma, with no malignant cells identified. Audiogram demonstrated a mean hearing loss of 65 dB on the right ear and an air-bone gap of 45 dB. Review of literature was also performed on giant cholesteatoma.

Interventions
He underwent a modified Fisch Type B infratemporal fossa approach to completely remove the cholesteatoma and a vascularized free flap was utilized to fill the surgical defect.

Main Outcome Measures
Complete extirpation of choles-teatoma and resolution of otorrhoea.

Results
Repeat imaging showed complete removal of cholesteatoma and clinically there was resolution of the otorrhea. Review of the literature has shown a lack of consensus around the definition of giant cholesteatoma. Most cases in the literature demonstrated extensive involvement of anatomical spaces beyond the confines of the temporal bone to qualify for the diagnosis of giant cholesteatoma.

Conclusions
Giant cholesteatoma should be suspected in cases of recurrent ear discharge following canal wall down mastoidectomy. The case we report add to the literature to benefit future patients in preoperative counseling and better inform management.
Hearing Loss in Adults With Alström Syndrome—Experience From the UK National Alström Service
Authors: Quoraishi Sadik , Mason Gemma , Geberhiwot Tarekegn , Dalton Claudia Lucy 
Published: June 2022

Objective
To characterize the patterns of hearing loss and methods of hearing rehabilitation in the UK national cohort of adults with Alström syndrome.

Study Design
Retrospective review of electronic patient records.

Setting
UK National multi-disciplinary team (MDT) Alström service held at the Queen Elizabeth Hospital, Birmingham.

Patients
Forty one adult patients with a diagnosis of Alström syndrome, confirmed via ALMS1 gene sequencing, are under ongoing review within the UK National MDT Alström service.

Main Outcome Measures
Magnitude and type of hearing loss were analyzed using patients’ audiometric data. Deterioration of hearing was calculated using serial pure tone audiograms. Methods of hearing rehabilitation used by patients and potential candidacy for cochlear implantation were analyzed.

Results
Of 34 patients with available audiograms, all had sensorineural hearing loss (SNHL). Dual sensory (visual and hearing) loss was present in 32/34 (94%) patients. Hearing deteriorated with advancing age, at 1.23 dB/yr. Severe- profound SNHL was present in 9/34 (26%) cases. Air conduction hearing aids were used in 27/34 (79%) cases, and cochlear implants in 2/34 (5%).

Conclusions
Alström syndrome is an ultra-rare genetic disorder with progressive, debilitating multi-system manifestations, including SNHL. The UK National MDT Alström service represents one of the largest reported adult cohorts in the world. SNHL in this group was ubiquitous, showing a rapid decline in hearing with age. Annual audiometric assessment to enable early diagnosis of hearing loss and optimum rehabilitation are paramount to minimize the impact of hearing loss in this condition.
Statistical Shape Model of the Temporal Bone Using Segmentation Propagation
Authors: Ding Andy S. , Lu Alexander , Li Zhaoshuo , Galaiya Deepa , Ishii Masaru , Siewerdsen Jeffrey H. , Taylor Russell H. , Creighton Francis X. 
Published: June 2022

Hypothesis
Automated image registration techniques can successfully determine anatomical variation in human temporal bones with statistical shape modeling.

Background
There is a lack of knowledge about inter-patient anatomical variation in the temporal bone. Statistical shape models (SSMs) provide a powerful method for quantifying variation of anatomical structures in medical images but are time-intensive to manually develop. This study presents SSMs of temporal bone anatomy using automated image-registration techniques.

Methods
Fifty-three cone-beam temporal bone CTs were included for SSM generation. The malleus, incus, stapes, bony labyrinth, and facial nerve were automatically segmented using 3D Slicer and a template-based segmentation propagation technique. Segmentations were then used to construct SSMs using MATLAB. The first three principal components of each SSM were analyzed to describe shape variation.

Results
Principal component analysis of middle and inner ear structures revealed novel modes of anatomical variation. The first three principal components for the malleus represented variability in manubrium length (mean: 4.47 mm; ±2-SDs: 4.03–5.03 mm) and rotation about its long axis (±2-SDs: -1.6° to 1.8° posteriorly). The facial nerve exhibits variability in first and second genu angles. The bony labyrinth varies in the angle between the posterior and superior canals (mean: 88.9°; ±2-SDs: 83.7°–95.7°) and cochlear orientation (±2-SDs: -4.0° to 3.0° anterolaterally).

Conclusions
SSMs of temporal bone anatomy can inform surgeons on clinically relevant inter-patient variability. Anatomical variation elucidated by these models can provide novel insight into function and pathophysiology. These models also allow further investigation of anatomical variation based on age, BMI, sex, and geographical location.
Comparative efficacy trials in inflammatory bowel disease: current and future implications for practice
Authors: Ahuja Dhruv , Singh Siddharth 
Published: June 2022

Purpose of review
Over the last decade, there has been rapid expansion of the therapeutic armamentarium, and evolution of treatment strategies, for the management of inflammatory bowel diseases (IBDs). Consequently, there is an increasing need for head-to-head or comparative efficacy trials to inform optimal positioning of therapies, and pragmatic trials comparing treatment strategies to inform treatment approach. In this review, we will discuss the current status and future of comparative efficacy clinical trials in IBD.

Recent findings
Pivotal phase IIIB superiority clinical trials have demonstrated superiority of vedolizumab over adalimumab for achieving clinical remission in patients with moderate-to-severe ulcerative colitis (VARSITY) and failed to demonstrate superiority of ustekinumab over adalimumab in patients with moderate-to-severe Crohn's disease (SEAVUE). Noninferiority clinical trials of biosimilars have confirmed absence of meaningful differences in safety and efficacy of biosimilar infliximab over originator infliximab, as initial therapy or switching stable patients during maintenance. Network meta-analyses, indirect treatment comparison using patient-level data from placebo-controlled trials and real-world observational studies have inform comparative effectiveness and safety of different therapies for management of IBD.

Summary
Head-to-head clinical trials are critically important to advance the field of IBD. Comparative efficacy trials are slow and expensive to conduct, may not be broadly generalizable, and are not powered for safety events or other relevant outcomes. Alternative approaches to comparative effectiveness such as network meta-analysis and well designed real-world observational studies are able to bridge gaps in clinical practice.