bluuebunny/crossref_metadata_2025 huggingface dataset:
Tackling climate change and health inequalities in primary care
Authors: Blane David N , Basu Nayanika
Published: December 2022

The Climate Emergency is now widely accepted as the biggest public health crisis facing humanity. Previous research has highlighted how social and health inequalities shape the health impacts of climate change in the UK, but there has been little attention to the role of general practice in deprived areas. This Brief Report summarises a roundtable discussion of Scottish ‘Deep End’ GPs - family doctors working in the most socio-economically deprived areas - which took place weeks before the 26th UN Climate Change Conference (COP26), held in Glasgow in November 2021. The report highlights the need for urgent action to make general practice more sustainable, including recommendations for community engagement, (de)prescribing, medical education, digital inclusion, and investment in premises and capacity building.
The Relationship of Age-Related Hearing Loss with Cognitive Decline and Dementia in a Sinitic Language-Speaking Adult Population: A Systematic Review and Meta-Analysis
Authors: Fu Xinxing , Eikelboom Robert H , Tian Rong , Liu Bo , Wang Shuo , Jayakody Dona M P
Published: December 2022

Background and Objectives

Substantial evidence supports the association between untreated hearing loss, cognitive decline, and dementia in the non-tonal language-speaking population. Whether a similar association between hearing loss and cognitive decline and dementia exists in Sinitic tonal language-speaking people is yet to be elucidated. We aimed to systematically review the current evidence on the association between hearing loss and cognitive impairment/decline, and dementia in older adults who speak a Sinitic tonal language.

Research Design and Methods

This systematic review considered peer-reviewed articles that employed objective or subjective hearing measurement and cognitive function, cognitive impairment, or diagnosis of dementia. All articles written in English and Chinese and published before March 2022 were included. Databases including Embase, MEDLINE, Web of Science, PsycINFO and Google Scholar, SinoMed, and CBM were utilized using MeSH terms and keywords.

Results

Thirty-five articles met our inclusion criteria. Of these, 29 unique studies with an estimated 372,154 participants were included in the meta-analyses. Among all included studies, the effect size of cognitive function with hearing loss, the regression coefficient was −0.26 (95% confidence interval [CI], −0.45 to −0.07). Among cross-sectional and cohort studies, a significant association was found between hearing loss and cognitive impairment and dementia, with odds ratios of 1.85 (95% CI, 1.59–2.17) and 1.89 (95% CI, 1.50–2.38), respectively.

Discussion and Implications

Most of the studies included in this systematic review observed a significant association between hearing loss and cognitive impairment and dementia. There was no significant difference to the findings in non-tonal language populations.
Improved anisotropy of magnetic remanence results from vectorial readings using novel refinement method
Authors: Wack Michael R
Published: December 2022

Anisotropy of magnetic remanence (AMR) is typically obtained by imparting a remanence through a sequence of reference directions and subsequent measurement of the remanent magnetic moment with a separate device. This gives rise to potential misalignments which can affect the resultant anisotropy tensor. Vectorial measurements from rock magnetometers are favourable to obtain the best estimate of the anisotropy tensor but make the results highly dependent on the exact knowledge of the reference directions. This can be partly overcome by using the projection of the remanence vector on the reference direction instead of using the full vector in the calculation of the best-fitting anisotropy tensor. Since AMR experiments are laborious, it is troublesome to compensate the loss in information with additional measurements. This paper demonstrates an iterative refinement method to recover the original reference directions and therefore to improve the results of AMR experiments by using full vectorial readings. The method works well with a six-axis protocol for misalignment of the reference directions up to 25° and for degrees of anisotropy up to 250 per cent, which covers most experimental and geological cases.
Knowledge of sexual consent as a protective factor against sexual violence perpetration among first-year college men: a moderation analysis
Authors: Schipani-McLaughlin A M , Leone R M , Salazar L F , Swahn M H , Khader S
Published: December 2022

This study examined whether knowledge of sexual consent buffers the relationship between risk factors for sexual violence (SV) and SV perpetration among first-year college men. The study data were drawn from a longitudinal study with 1144 first-year college men. A series of generalized linear models were conducted to examine whether knowledge of sexual consent moderated the relationship between SV risk factors and SV perpetration. Knowledge of sexual consent moderated the effect of hypermasculinity (P < 0.001), binge drinking (P < 0.001), rape-supportive social norms (P = 0.007) and peer support for SV (P < 0.001) such that there was a positive association between risk factors and SV perpetration among those with lower, but not higher, knowledge of sexual consent. Knowledge of sexual consent did not significantly moderate the relationship between SV perpetration and outcome expectancies for non-consensual sex (P = 0.387) and pornography use (P = 0.494). Knowledge of sexual consent may counteract risk factors for SV perpetration among young college men. The findings highlight the need for consent education to be incorporated in youth comprehensive sexual education to increase knowledge of sexual consent prior to college and campus-based SV prevention programming delivered to college students.
Optimizing the Application Timing and Dosage ofMetarhizium brunneum(Hypocreales: Clavicipitaceae) as a Biological Control Agent ofAedes aegypti(Diptera: Culicidae) Larvae
Authors: Alkhaibari A M , Wood M J , Yavasoglu S I , Bull J C , Butt T M
Published: December 2022

Aedes aegypti (Diptera: Culicidae) is the principal vector of dengue and other viruses that cause disease among 100 to 400 million people each year. The recent development of widespread insecticidal resistance has led to the rapid development of biological control solutions aimed at larval control. While the efficacy of Metarhizium brunneum has been shown against Aedes larvae, the impact of larval population dynamics will need to be determined to formulate effective control strategies. In this study, larvae were subjected to four concentrations of M. brunneum (105, 106, 107, 108 conidia ml−1). Larvae were found to be susceptible to M. brunneum with dose-dependent efficacy. When constant larval immigration was added as a parameter, peak mortality was consistently found to occur on the fourth day, before a significant reduction in control efficacy linked to a decline in conidial availability within the water column. This suggests that M. brunneum treatments should be applied at a concentration 1 × 107 conidia ml−1 every four days to effectively control mosquito larvae in the field, regardless of the fungal formulation, water volume, or larval density. Understanding fungal-mosquito dynamics is critical in developing appropriate control programs as it helps optimize the fungal control agent’s dose and frequency of application.
Case report: renal cell carcinoma metastasis to the tongue
Authors: Walsh Michael A , Quinn Alanna J , Mahesh Bangalore
Published: December 2022

Tongue metastasis of renal cell carcinoma (RCC) are rare, with 90% of malignant lesions in the oral cavity consisting of squamous cell carcinoma (SCC). There are a number of subtypes of SCC which need to be considered as well as rarer pathology and even benign conditions. The case involves a 63-year-old gentleman with an incidental finding of pulmonary metastasis from a RCC of the left kidney, and he concurrently had a RCC deposit on the dorsum of the tongue, which was diagnosed after biopsy. Treatment modalities of surgical excision, radiotherapy and systemic therapy are considered, but with such a poor prognosis with disseminated disease, options are limited. Treatment should include multidisciplinary team input, with a focus on reducing disease morbidity.
A rare case of colo-salpingeal fistula complicating acute sigmoid diverticulitis
Authors: Jangam Aishwarya , Gillespie Christopher
Published: December 2022

Colo-salpingeal fistulae due to acute diverticulitis are rare entities. A 65-year-old female with a 5-day history of left iliac fossa pain, fevers and diarrhoea was seen in a metropolitan hospital. Initial computed tomography of the abdomen and pelvis characterized a left tubular adnexal structure with an air fluid level and normal-appearing colon and was reported as pyosalpingitis. Worsening sepsis despite antibiotics prompted further imaging where thickening of the sigmoid colon was noted, and the provisional diagnosis was revised to complicated acute diverticulitis with perforation into the left fallopian tube/ovary. This was managed with a laparoscopic anterior resection and en bloc left salpingo-oopherectomy, and was followed by an uneventful recovery. The presence of a gas-containing collection remains a sensitive imaging sign for the presence of an enteric fistula and a high index of suspicion should be maintained when this is encountered.
Virtual fracture clinics: be vigilant for the ligamentous elbow injury
Authors: Robertson-Waters Eve E , Cuthbert Rory , Van Rensburg Lee
Published: December 2022

The Covid-19 pandemic encouraged remote healthcare and led to dependency on virtual fracture clinics (VFC). VFC are orthopaedic consultant-led clinics where cases are reviewed virtually following referral by emergency department clinicians. Success is contingent on a comprehensive initial history and examination. This pathway has high patient satisfaction rates and cost-saving benefits. However, clinicians must be vigilant for high-energy mechanisms or examination findings suggestive of greater underlying injury. In this case, VFC missed a rare ipsilateral annular ligament injury in a 15-year old with an undisplaced radial neck fracture, following a fall from a horse. This led to radial head dislocation and delayed surgical repair. Untreated, radial head dislocations lead to pain and reduced range of movement. Despite the rarity of this injury pattern, face-to-face orthopaedic examination would have raised concern for significant ligamentous injury. A high-energy mechanism of injury mandates face-to-face senior orthopaedic review to avoid missing serious concomitant injury.
A case of primary infertility and a patient with ventriculoperitoneal shunt
Authors: Eliasi Elior , Cohen Adiel , Wasser Oren , Oelsner Gabriel
Published: December 2022

Ventriculoperitoneal (VP) shunts are the main treatment modality for patients with hydrocephalus. The complications arising in patients with VP shunts are well documented. We present a case of infertility in a patient with a long-standing VP shunt. Her infertility is thought to be the result of pelvic adhesions due to factors related to the distal end of her VP shunt. A 22-year-old female with a 1-year history of infertility was referred due to bilateral hydrosalpinges. Diagnostic laparoscopy revealed multiple adhesions surrounding the distal end of the fallopian tubes. The distal portion of a VP shunt, which was placed over the course of her childhood, was found to be grossly inflamed and densely adherent to the pelvic viscera. VP shunts may produce abdominal adhesions and can cause mechanical infertility.
A huge retroperitoneal cyst with a rare clinical presentation
Authors: Alqaisi Hayder , Wanders Alkwin , Naujokaite Gintare , Pedersen Lasse
Published: December 2022

A 39-year-old male presented with deep venous thrombosis in the right lower limb. He had been experiencing increasing abdominal girth over several years, but this went undetected at the initial examination. Eighteen months later, a computed tomography was conducted, showing a huge retroperitoneal cyst (25 × 23 × 16 cm) lifting the right external iliac vessels. Complete surgical excision of the cyst was performed. The cyst was unilocular and contained 5 l of clear fluid. Histopathology examination found a thin cyst wall consisting of fibrous stromal tissue with a single-layer epithelium lining. Immunohistochemical staining revealed positivity for endothelial cell markers, CD31 and CD34, but negativity for the lymphatic marker podoplanin (D2–40), corresponding to a vascular origin, likely a venous malformation.
Pan-chromatic photometric classification of supernovae from multiple surveys and transfer learning for future surveys
Authors: Burhanudin Umar F , Maund Justyn R
Published: December 2022

Time-domain astronomy is entering a new era as wide-field surveys with higher cadences allow for more discoveries than ever before. The field has seen an increased use of machine learning and deep learning for automated classification of transients into established taxonomies. Training such classifiers requires a large enough and representative training set, which is not guaranteed for new future surveys such as the Vera Rubin Observatory, especially at the beginning of operations. We present the use of Gaussian processes to create a uniform representation of supernova light curves from multiple surveys, obtained through the Open Supernova Catalog for supervised classification with convolutional neural networks. We also investigate the use of transfer learning to classify light curves from the Photometric LSST Astronomical Time Series Classification Challenge (PLAsTiCC) data set. Using convolutional neural networks to classify the Gaussian process generated representation of supernova light curves from multiple surveys, we achieve an Area Under the Receiver Operating Characteristic curve (AUC) score of 0.859 for classification into Types Ia, Ibc, and II. We find that transfer learning improves the classification accuracy for the most under-represented classes by up to 18 per cent when classifying PLAsTiCC light curves, and is able to achieve an AUC score of 0.946 ± 0.001 when including photometric redshifts for classification into six classes (Ia, Iax, Ia-91bg, Ibc, II, and SLSN-I). We also investigate the usefulness of transfer learning when there is a limited labelled training set to see how this approach can be used for training classifiers in future surveys at the beginning of operations.
Multiband optical variability of the TeV blazar PG 1553 + 113 in 2019
Authors: Dhiman Vinit , Gupta Alok C , Kurtanidze Sofia O , Eglitis I , Strigachev A , Damljanovic G , Wiita Paul J , Gu Minfeng , Gaur Haritma , Vince Oliver , Bachev R , Bisen D P , Ibryamov S , Ivanidze R Z , Jovanovic Miljana D , Kurtanidze Omar M , Nikolashvili M G , Semkov E , Spassov B , Stojanovic M , Villarroel Beatriz , Xu Haiguang , Zhang Zhongli
Published: December 2022

We report the flux and spectral variability of PG 1553 + 113 on intra-night (IDV) to short-term time-scales using BVRI data collected over 91 nights from 28 February to 8 November 2019 employing 10 optical telescopes: three in Bulgaria, two each in India and Serbia, and one each in Greece, Georgia, and Latvia. We monitored the blazar quasi-simultaneously for 16 nights in the V and R bands and 8 nights in the V, R, I bands and examined the light curves (LCs) for intra-day flux and colour variations using two powerful tests: the power-enhanced F-test and the nested ANOVA test. The source was found to be significantly (>99 per cent) variable in 4 nights out of 27 in R-band, 1 out of 16 in V-band, and 1 out of 6 nights in I-band. No temporal variations in the colours were observed on IDV time-scale. During the course of these observations the total variation in R-band was 0.89 mag observed. We also investigated the spectral energy distribution (SED) using B-, V-, R-, and I-band data. We found optical spectral indices in the range of 0.878 ± 0.029 to 1.106 ± 0.065 by fitting a power law (Fν∝ν−α) to these SEDs of PG 1553 + 113. We found that the source follows a bluer-when-brighter trend on IDV time-scales. We discuss possible physical causes of the observed spectral variability.
The maximum extent of the filaments and sheets in the cosmic web: an analysis of the SDSS DR17
Authors: Sarkar Prakash , Pandey Biswajit , Sarkar Suman
Published: December 2022

Filaments and sheets are striking visual patterns in cosmic web. The maximum extent of these large-scale structures are difficult to determine due to their structural variety and complexity. We construct a volume-limited sample of galaxies in a cubic region from the SDSS, divide it into smaller subcubes and shuffle them around. We quantify the average filamentarity and planarity in the 3D galaxy distribution as a function of the density threshold and compare them with those from the shuffled realizations of the original data. The analysis is repeated for different shuffling lengths by varying the size of the subcubes. The average filamentarity and planarity in the shuffled data show a significant reduction when the shuffling scales are smaller than the maximum size of the genuine filaments and sheets. We observe a statistically significant reduction in these statistical measures even at a shuffling scale of $\sim 130 \, {{\, \rm Mpc}}$, indicating that the filaments and sheets in three dimensions can extend up to this length scale. They may extend to somewhat larger length scales that are missed by our analysis due to the limited size of the SDSS data cube. We expect to determine these length scales by applying this method to deeper and larger surveys in future.
Fundamental parameters for double-lined spectroscopic and detached eclipsing binary system J064726.39 + 223431.6
Authors: Kovalev Mikhail , Wang Song , Chen Xuefei , Han Zhanwen
Published: December 2022

We present a study of the detached eclipsing binary J064726.39 + 223431.6 using spectra from the LAMOST medium-resolution spectra and Transiting Exoplanet Survey Satellite photometry. We use full-spectrum fitting to derive radial velocities and spectral parameters: ${T_{\rm eff}}_{A,B}=6177,\, 5820$ K, $V \sin {i}_{A,B}=59,\, 50~\, {\rm km}\, {\rm s}^{-1}$, and [Fe/H]A,B = −0.19 dex. The orbital solution and light-curve analysis suggest that it is a close pair of fast rotating stars on a circular orbit. We measure their masses to be $M_{A,B}=1.307\pm 0.007,\, 1.129\pm 0.005\, \mathrm{M}_\odot$ and their radii to be $R_{A,B}=1.405\pm 0.052,\, 1.219\pm 0.060\, \mathrm{R}_\odot$, resulting in surface gravities of $\log {\rm (g)}_{A,B}=4.259\pm 0.033,\, 4.319\pm 0.042$ (cgs). Theoretical models cannot match all of these properties, predicting significantly higher Teff for a given metallicity. The derived age of the system is 1.56 Gyr, which indicates that both components are younger than Sun, which contradicts to much longer orbit’s circularization time-scale.
Evolution of the long-period pulsar PSR J0901−4046
Authors: Gençali A A , Ertan Ü , Alpar M A
Published: December 2022

The fallback disc model predicted that anomalous X-ray pulsars (AXPs) and soft gamma repeaters (SGRs) will evolve to isolated long-period pulsars (LPPs) before the discovery of the first two LPPs this year. Unlike normal radio pulsars, LPPs show transient pulsed-radio epochs with unusual and variable pulse shapes, similar to the radio behaviour of the few radio emitting AXP/SGRs. We show that the present properties of the recently discovered second LPP, PSR J0901−4046 (P ≃ 76 s), are obtained as a result of evolution in interaction with a fallback disc, as we had already shown for the first discovered LPP, GLEAM-X J162759.5−523504.3 (P ≃ 1091 s). While there is only an upper limit to the period derivative, $\dot{P}$, of GLEAM-X J162759.5−523504.3, the $\dot{P}$ of the PSR J0901−4046 has already been measured, providing better constraints for the evolutionary models. The model can produce the source properties with a dipole moment μ ≃ 1030 G cm3. The results are not sensitive to the initial pulsar period. Our results indicate that PSR J0901−4046 went through an AXP/SGR epoch at an age of a few 104 yr, and is ∼(6–8) × 105 yr old at present.
Integrated response analysis of pediatric low-grade gliomas during and after targeted therapy treatment
Authors: Tsai Jessica W , Choi Jungwhan John , Ouaalam Hakim , Murillo Efrain Aguilar , Yeo Kee Kiat , Vogelzang Jayne , Sousa Cecilia , Woods Jared K , Ligon Keith L , Warfield Simon K , Bandopadhayay Pratiti , Cooney Tabitha M
Published: December 2022

Background

Pediatric low-grade gliomas (pLGGs) are the most common central nervous system tumor in children, characterized by RAS/MAPK pathway driver alterations. Genomic advances have facilitated the use of molecular targeted therapies, however, their long-term impact on tumor behavior remains critically unanswered.

Methods

We performed an IRB-approved, retrospective chart and imaging review of pLGGs treated with off-label targeted therapy at Dana-Farber/Boston Children’s from 2010 to 2020. Response analysis was performed for BRAFV600E and BRAF fusion/duplication-driven pLGG subsets.

Results

Fifty-five patients were identified (dabrafenib n = 15, everolimus n = 26, trametinib n = 11, and vemurafenib n = 3). Median duration of targeted therapy was 9.48 months (0.12–58.44). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation were 62.1%, 38.2%, and 31.8%, respectively. Mean volumetric change for BRAFV600E mutated pLGG on BRAF inhibitors was −54.11%; median time to best volumetric response was 8.28 months with 9 of 12 (75%) objective RAPNO responses. Median time to largest volume post-treatment was 2.86 months (+13.49%); mean volume by the last follow-up was −14.02%. Mean volumetric change for BRAF fusion/duplication pLGG on trametinib was +7.34%; median time to best volumetric response was 6.71 months with 3 of 7 (43%) objective RAPNO responses. Median time to largest volume post-treatment was 2.38 months (+71.86%); mean volume by the last follow-up was +39.41%.

Conclusions

Our integrated analysis suggests variability in response by pLGG molecular subgroup and targeted therapy, as well as the transience of some tumor growth following targeted therapy cessation.
Optimal public debt indexation in advanced economies
Authors: Gomez-Gonzalez Patricia
Published: December 2022

This article examines the cross-country heterogeneity in the share of advanced economies’ inflation-linked (IL) debt when governments, taking inflation as given, issue IL debt and nominal debt and aim to minimize tax distortions, debt investors are risk-neutral, and nominal debt carries a convenience premium. The optimal IL debt share increases in the level and the variance of inflation, decreases in the correlation between government spending and inflation, and, for a fixed level of debt, decreases in the nominal debt’s convenience premium. Data between 1995 and 2018 for 14 advanced economies that issue IL debt exhibit cross-country correlations in line with the model’s comparative statics about inflation. The model’s welfare analysis suggests that nominal debt’s convenience premium can explain the relatively low public debt indexation in most advanced economies.
Posterior urethral polyp in a male child: a rare case report
Authors: Razzok Ali , Muhamad Muhamad Sinan , Ismaeel Ali , Alyousef Khaled , Oukan Majdy
Published: December 2022

Urethral polyps are one of the rare deformities of the urethra. In most cases, the urethral polyps would not be considered in the differential diagnosis process by a huge number of physicians, mainly owing to the rarity of documented cases in the medical literature and because of the wide variety of unspecified symptoms the urethral polyp might demonstrate. Urethral polyps are more common in males than in females, and they are usually diagnosed at an early age. Treatment options include transurethral resection, endoscopic suprapubic approach and open surgery. The disease prognosis is excellent as it does not usually recur after being completely removed and the risk of malignant transformation is very low. We are going to report a case of a 3-month-old boy who presented with bilateral vesicoureteral reflux and hydronephrosis, which revealed the presence of a large posterior urethral polyp.
Renal sarcoidosis associated with certolizumab pegol treatment for psoriatic arthritis
Authors: Hum Ryan M , Kanigicherla Durga A , Ho Pauline
Published: December 2022

We present a case of certolizumab-associated renal sarcoidosis, the first reported case in a patient with psoriatic arthritis (PsA) that was effectively treated with corticosteroids. A 55-year-old Caucasian man with PsA diagnosed at age 47 and plaque psoriasis since his early twenties was on certolizumab pegol (CZP) for 7 months before presenting to the emergency department with seizures and renal failure. A renal biopsy confirmed renal sarcoidosis. His CZP therapy was stopped, and after several months taking prednisolone at a reducing regime, his renal function improved, and his PsA remained under control. When considering further treatment options for his PsA keeping in mind that other drugs, especially tumour necrosis factor-alpha inhibitors, have been reported to be associated with sarcoidosis, tofacitinib was considered to be a future treatment option acceptable to the patient, given current National Institute for Health and Care Excellence guidelines approving its use in PsA and the lack of reports of tofacitinib-associated sarcoidosis in the literature.
A rare presentation of esotropia in high myopia in a young adult: a case report
Authors: Gupta Namrata , Pradhan Kishore R , Chopra Geeta , Khadka Sajina
Published: December 2022

Esotropia in myopia is an uncommon occurrence. Most common cause of esotropia in high myopic elderly is Heavy Eye Syndrome. An uncommon cause in young adults is Acute Acquired Comitant Esotropia often associated with excessive indulgence in near work. A 21 year old male patient presented with diplopia for one year, more for distance than near and spent more than 8-10 hours for near tasks. Unaided visual acuity in BE was 2/60 and was 6/9 in RE and 6/6 in LE with correction. Prism base cover test revealed 25 BO PD for distance and 20 BO PD for near. Diplopia was seen in all position of gaze. Right Eye Lateral rectus resection 8 mm was done and HPE report revealed features of Lateral rectus Muscle atrophy. It is important to understand the pathogenesis of this entity and consider other possible causes of esotropia in myopia. Key words: Myopia, Esotropia, Comitant, Diplopia.
A case of Takayasu arteritis complicated with pulmonary infarction
Authors: Hirayama Takehiro , Morita Takayoshi , Funakoshi Kenji , Yoshimine Yuko , Minoda Saki , Murakami Teruaki , Okita Yasutaka , Narazaki Masashi , Kumanogoh Atsushi
Published: December 2022

Takayasu arteritis (TAK) is a vasculitis that causes inflammation in the arterial walls of large blood vessels. The complication rate of pulmonary artery lesion in TAK has been reported to be relatively high. Severe pulmonary artery stenosis can cause pulmonary infarction in rare cases. A 48-year-old woman had experienced cough and fever persistently for 3 months and visited a city hospital. Contrast-enhanced computed tomography (CT) and positron emission tomography (PET)-CT scans revealed TAK complicated with left pulmonary artery lesion. Contrast-enhanced CT couldn’t detect wall thickening in the left smaller bifurcated pulmonary artery branch, but PET-CT did reveal this inflammation. Several weeks after we initiated treatment with high-dose prednisolone, the patient’s symptoms and inflammatory findings disappeared. PET-CT may be useful for evaluating the inflammation of the pulmonary artery in TAK, and high-dose steroid monotherapy as induction therapy may be effective for TAK complicated with pulmonary artery lesions causing pulmonary infarction.
A case of percutaneous coronary intervention of the right coronary artery in a situs inversus patient with foreshortening of lesion revealed by intravenous ultrasound imaging technology
Authors: Kager Rebecca L , Vacek Thomas P
Published: December 2022

Situs inversus totalis is a rare anomaly in which the internal organs are transposed oppositely as mirror images. Due to its rarity, interventionalists are less likely to be acquainted with angiography in this unique population. In the case of lesion ambiguity, different invasive diagnostic tools can be used to further evaluate lesion severity, including fractional flow reserve, instantaneous wave-free ratio and intravenous ultrasound (IVUS). In this case, we discuss the usefulness of IVUS as a beneficial tool in evaluation of angiographically ambiguous lesions due to foreshortening. Dextrocardia presents unique challenges to the interventional cardiologist secondary to difficulty in acquiring adequate views and unfamiliarity with mirroring of anatomy, and thus angiography can result in inaccurately assessed lesions. We demonstrate how IVUS can be used in evaluation of such lesions for more accurate evaluation, precision in stent placement and in turn better patient outcomes.
Circ-ABCC4 contributes to prostate cancer progression and radioresistance by mediating miR-1253/SOX4 cascade
Authors: Yu Tao , Du Hong , Sun Changhai
Published: December 2022

Circular RNAs (circRNAs) exert pivotal functions in many malignancies. However, the roles of circ-ABCC4 in prostate cancer (PCa) radioresistance and progression remain largely unclear. Cell viability, proliferation, apoptosis, invasion, and radioresistance were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2’-deoxyuridine, flow cytometry, transwell invasion, and colony formation assays. Tumor xenograft experiment was conducted to assess circ-ABCC4 role in xenograft growth in vivo. Dual-luciferase reporter assay was implemented to test the target relation of microRNA-1253 (miR-1253) and circ-ABCC4 or SRY-box transcription factor 4 (
SOX4
). Circ-ABCC4 enrichment was prominently raised in PCa tissue specimens and cells. Circ-ABCC4 depletion blocked PCa cell viability, proliferation, invasion, and radioresistance and triggered apoptosis. Circ-ABCC4 silencing aggravated irradiation-induced inhibitory effect on xenografts growth. miR-1253 was a downstream molecule of circ-ABCC4, and circ-ABCC4 depletion-mediated anti-cancer impacts in PCa cells were partly counteracted by decreasing miR-1253 abundance. miR-1253 targeted SOX4 mRNA, and miR-1253 blocked PCa cell malignant phenotypes partly by targeting SOX4. Circ-ABCC4 could enhance SOX4 abundance by absorbing miR-1253. Circ-ABCC4 exerted a pro-tumor activity by facilitating PCa cell viability, proliferation, invasion, and radioresistance and suppressing apoptosis.
Aspirin for primary prevention of cardiovascular disease in women
Authors: Lau Emily S.
Published: December 2022

Aspirin use for primary prevention of cardiovascular disease is controversial. Low-dose aspirin may be considered for primary prevention in women on an individualized basis for those aged 40 to 59 years with a 10-year cardiovascular risk of 10% or more and without increased bleeding risk. Low-dose aspirin for primary prevention is not advised for low-risk women or women aged 60 years or older.
Children who are HIV-exposed and uninfected: evidence for action
Authors: Prendergast Andrew J. , Evans Ceri
Published: December 2022

Prior to widespread availability of antiretroviral therapy (ART) in sub-Saharan Africa, children who were HIV-exposed but uninfected (HEU) had increased mortality, morbidity and undernutrition compared with children who were HIV-unexposed. Scale-up of ART has led to impressive declines in vertical HIV transmission, but over 15 million children are now HEU, 90% of whom live in sub-Saharan Africa. There are ongoing health disparities among children who are HEU, with higher mortality, morbidity and stunting and modest impairments in early child development, which collectively hamper health and human capital in high prevalence countries. The underlying causes are multifactorial and include exposure to HIV, co-infections and a skewed antenatal inflammatory milieu, particularly if mothers start ART once they have advanced disease, as well as socioeconomic risk factors, which may cluster in HIV-affected households. Improving maternal health through early and sustained ART, ensuring optimal breastfeeding, and implementing evidence-based priority interventions for all children in areas of high HIV prevalence, will likely improve outcomes. A more comprehensive intervention package based on the Nurturing Care Framework may have particular benefits for children who are HEU, to close health gaps and ensure that the next generation of HIV-free children survive and thrive, and lead healthy and productive lives.
Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study
Authors: Hanttu Anna M. , Pekkala Satu , Satokari Reetta , Hartikainen Anna K. , Arkkila Perttu , Pietiläinen Kirsi H. , Sutinen Jussi P.
Published: December 2022

Objective:

To study gut microbiota before and 24 weeks after a single antiretroviral agent switch.

Design:

HIV-positive patients with efavirenz (EFV) or a protease inhibitor (PI)-based antiretroviral therapy (ART) were randomized to switch EFV or PI to raltegravir (RAL group, n = 19) or to continue unchanged ART (EFV/PI group, n = 22). Age and weight-matched HIV-negative participants (n = 10) were included for comparison.

Methods:

Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected.

Results:

At week 24, microbiota diversity (Chao1 index) was higher in RAL than the EFV/PI group (P = 0.014), and RAL group did not differ from HIV-negative participants. In subgroup analysis switching from EFV (P = 0.043), but not from a PI to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P = 0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P = 0.01 and P = 0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged.

Conclusion:

Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.
Evolutionary conservation and divergence of the transcriptional regulation of bivalve shell secretion across life-history stages
Authors: Cavallo Alessandro , Clark Melody S. , Peck Lloyd S. , Harper Elizabeth M. , Sleight Victoria A.
Published: December 2022

Adult molluscs produce shells with diverse morphologies and ornamentations, different colour patterns and microstructures. The larval shell, however, is a phenotypically more conserved structure. How do developmental and evolutionary processes generate varying diversity at different life-history stages within a species? Using live imaging, histology, scanning electron microscopy and transcriptomic profiling, we have described shell development in a heteroconchian bivalve, the Antarctic clam,Laternula elliptica,and compared it to adult shell secretion processes in the same species.Adult downstream shell genes, such as those encoding extracellular matrix proteins and biomineralization enzymes, were largely not expressed during shell development. Instead, a development-specific downstream gene repertoire was expressed. Upstream regulatory genes such as transcription factors and signalling molecules were largely conserved between developmental and adult shell secretion. Comparing heteroconchian data with recently reported pteriomorphian larval shell development data suggests that, despite being phenotypically more conserved, the downstream effectors constituting the larval shell ‘tool-kit’ may be as diverse as that of adults. Overall, our new data suggest that a larval shell formed using development-specific downstream effector genes is a conserved and ancestral feature of the bivalve lineage, and possibly more broadly across the molluscs.
Elucidation of reactive oxygen species scavenging pathways of norbergenin utilizing DFT approaches
Authors: Haq Kautsar Ul , Rusdipoetra Rahmanto Aryabraga , Siswanto Imam , Suwito Hery
Published: December 2022

Bergenin is a polyphenolic compound that contains isocoumarin skeletal derived from
C
-glycosylated 4-
O
-methylgallic acid. The biological activities of this compound and its derivatives are quite diverse. Recent studies reveal neuroprotective effects
in vitro
and
in vivo
in Alzheimer's. Norbergenin is a demethylated form of bergenin, known for better antioxidant capacity and associated with neuroprotective properties through oxidative stress inhibition. This study focused on investigating the scavenging mechanism of norbergenin with the
•
OH,
•
OOH, and

O

2

∙
−

as a radical model under physiological and lipid environments. The thermodynamic and kinetic parameters of the hydrogen transfer (HT), single electron transfer (SET), sequential proton lost-electron transfer (SPLET) and radical adduct formation (RAF) mechanisms were determined theoretically by the density functional theory (DFT) at M06-2X/6-311 + + G(d,p) level of theory. Based on the computational results, this compound has proved as an excellent
•
OOH and
•
OH scavenger under physiological conditions better than Trolox and vitamin C, whereas its radical demonstrated as an efficient

O

2

∙
−

scavenger.
Elastic contact of random surfaces with fractal and Hurst effects
Authors: Jetti Yaswanth Sai , Ostoja-Starzewski Martin
Published: December 2022

Most of the recent research on random surface contact mechanics has been on self-affine surfaces. In such models, the fractal dimension (which represents the ‘roughness’) and the Hurst parameter (which represents the ‘spatial memory’) are linearly dependent. In this study, we investigate the non-adhesive, frictionless contact between elastic solids with non-self-affine manifolds. In particular, we use Cauchy and Dagum covariance functions, which can decouple the fractal and Hurst effects, to describe the height distribution of the random surfaces. A numerical model based on the Boussinesq point load fundamental solutions is employed along with the discrete convolution FFT method to perform the contact analysis. We investigate the true contact area evolution under increasing load for surfaces with a wide range of fractal and Hurst parameters. It is observed that the contact area evolution at light loads is almost independent of the Hurst parameter and non-monotonically dependent on the fractal dimension. By contrast, previous studies predicted the contact evolution to be weakly dependent on the Hurst parameter and the fractal dimension. The curvature of the plots of the slope of the contact area evolution is found to depend on the fractal dimension, contrary to previous studies, which predicted either convexity or concavity.
Ergosterol extraction: A comparison of methodologies
Authors: Wilkes Thomas I
Published: December 2022

Ergosterol is a component of the cell membrane of mycorrhizal fungi and is frequently used to quantify their biomass. Arbuscular mycorrhizal (AM) fungi and ectomycorrhizal (ECM) fungi establish a symbiotic relationship with a respective host plant. Several methods are currently employed for quantification of ergosterol; however, these utilise a series of potentially hazardous chemicals with a varying degree of exposure times to the user. The present method comparative study aims to ascertain the most reliable method to extract ergosterol whilst limiting hazard exposure to the user. Chloroform, cyclohexane, methanol and methanol hydroxide extraction protocols were applied to a total of 300 samples of root samples and a further 300 growth substrate samples across all protocols. Extracts were analysed via HPLC methodologies. Chromagraphic analysis showed chloroform based extraction procedures produced a consistently higher concentration of ergosterol in both root and growth substrate samples. Methanol hydroxide, without the addition of cyclohexane, produced very low concentration of ergosterol, with a reduction of quantified ergosterol of between 80 and 92% compared to chloroform extractions. Hazard exposure was greatly reduced following chloroform extraction protocol when compared with other extraction procedures.
SGC-CLK-1 (CAF-170) a chemical probe for the Cdc2-Like kinases CLK1, CLK2, and CLK4
Authors: Tiek Deanna , Wells Carrow I. , Schröder Martin , Song Xiao , Alamillo-Ferrer Carla , Goenka Anshika , Iglesia Rebeca , Lu Minghui , Hu Bo , Kwarcinski Frank , Sintha Parvathi , de Silva Chandi , Hossain Mohammad Anwar , Picado Alfredo , Zuercher William , Zutshi Reena , Knapp Stefan , Riggins Rebecca B. , Cheng Shi-Yuan , Drewry David H.
Published: December 2022

Small molecule modulators are important tools to study both basic biology and the complex signaling of protein kinases. The cdc2-like kinases (CLK) are a family of four kinases that have garnered recent interest for their involvement in a diverse set of diseases such as neurodegeneration, autoimmunity, and many cancers. Targeted medicinal chemistry around a CLK inhibitor hit identified through screening of a kinase inhibitor set against a large panel of kinases allowed us to identify a potent and selective inhibitor of CLK1, 2 and 4. Here, we present the synthesis, selectivity, and potential binding site of this compound – SGC-CLK-1. We further show CLK2 has the highest binding affinity, and high CLK2 expression correlates with a lower IC50in a screen of multiple cancer cell lines. Finally, we show that SGC-CLK-1 not only reduces serine arginine rich (SR) protein phosphorylation, but also alters SR protein and CLK2 subcellular localization in a reversible way. Therefore, we anticipate that this compound will be a valuable tool for increasing our understanding of CLKs and their targets, SR proteins, at the level of phosphorylation and subcellular localization.
Wolbachiaendosymbionts manipulate GSC self-renewal and differentiation to reinforce host fertility
Authors: Russell Shelbi L , Castillo Jennie Ruelas , Sullivan William T
Published: December 2022

The alphaproteobacteriumWolbachia pipientisinfects arthropod and nematode species worldwide, making it a key target for host biological control.Wolbachia-driven host reproductive manipulations, such as cytoplasmic incompatibility (CI), are credited for catapulting these intracellular bacteria to high frequencies in host populations. Positive, perhaps mutualistic, reproductive manipulations also increase infection frequencies, but are not well understood. Here, we identify molecular and cellular mechanisms by whichWolbachiainfluences the molecularly distinct processes of GSC self renewal and differentiation. We demonstrate thatwMel infection rescues the fertility of flies lacking the translational regulatormei-P26, and is sufficient to sustain infertile homozygousmei-P26-knockdown stocks indefinitely. Cytology revealed thatwMel mitigates the impact ofmei-P26loss through restoring proper pMad, Bam, Sxl, and Orb expression. In OreR files with wild-type fertility,wMel infection elevates lifetime egg hatch rates. Exploring these phenotypes through dual-RNAseq experiments revealed thatwMel infection rescues and offsets many gene expression changes induced bymei-P26loss at the mRNA level. Overall, we show thatwMel infection beneficially reinforces host fertility at mRNA, protein, and phenotypic levels, and these mechanisms may promote the emergence of mutualism and the breakdown of host reproductive manipulations.

Graphical Abstract

Highlights

●

The wMel strain ofWolbachiarestores fertility in females and males deficient for the essential translational regulatormeiotic-P26

●

Mei-P26’sgermline maintenance and oocyte cyst differentiation functions are genetically rescued by wMel infection

●

Perturbed pMad, Sxl, Bam, and Orb protein expression are mitigated by wMel infection

●

wMel infection elevates lifetime egg lay and hatch rates in OreR flies

●

Ovary transcriptomes reveal wMel infection restores or offsets changes in gene expression induced by the loss of functionalmei-P26

Significance Statement

Wolbachiabacterial symbionts are being harnessed as biological control agents through the use of their costly manipulations to host fertility. Here, we reveal that thewMel strain can have a beneficial impact on fruit fly development in both mutant and wild-type flies. This phenotype is essential to the long-term use of these bacteria for host population control.
Ultra-long-acting refillable nanofluidic implant confers full protection against SHIV infection in non-human primates
Authors: Pons-Faudoa Fernanda P. , Trani Nicola Di , Capuani Simone , Campa-Carranza Jocelyn Nikita , Nehete Bharti , Sharma Suman , Shelton Kathryn A. , Bushman Lane R. , Abdelmawla Farah , Williams Martin , Roon Laura , Nerguizian David , Xuan Chua Corrine Ying , Ittmann Michael M. , Nichols Joan E. , Kimata Jason T. , Anderson Peter L. , Nehete Pramod N. , Arduino Roberto C. , Grattoni Alessandro
Published: December 2022

The impact of pre-exposure prophylaxis (PrEP) on slowing the global human immunodeficiency virus (HIV) epidemic hinges on effective drugs and delivery platforms. Oral regimens have represented the pillar of HIV PrEP for years. However, variable adherence has spurred development of long-acting delivery systems, which also aim at increasing PrEP access, uptake and persistence. Here we present an ultra-long-acting and transcutaneously refillable subcutaneous nanofluidic implant for constant and sustained release of islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, for HIV PrEP. In rhesus macaques, the ISL-eluting implants (nISL) achieved constant plasma ISL levels (median 3.14 nM) and peripheral blood mononuclear cells (PBMCs) ISL-triphosphate levels (ISL-TP) (median 0.16 pmol/106cells) for over 20 months uninterrupted. These drug concentrations are above the established PrEP protection threshold. In two non-blinded, placebo-controlled studies with repeated low-dose rectal and vaginal SHIVSF162P3challenges in male and female rhesus macaques, respectively, nISL implants conferred 100% protection against infection (p=0.0005 and 0.0009, respectively between nISL and placebo control groups). The nISL implants were well tolerated with mild local tissue inflammation and no signs of systemic toxicity over the 20-month period. Overall, our refillable nISL implant is a promising ultra-long-acting delivery technology for HIV PrEP.

One Sentence Summary

An ultra-long-acting and subcutaneous refillable nanofluidic implant achieved preventive levels of islatravir in non-human primates for 20 months without refilling and conferred 100% protection against rectal and vaginal SHIV transmission.