bluuebunny/crossref_metadata_2025 huggingface dataset:
Radial Nerve Fascicular Transfer Preserving Long Head through Anterior Incision for Transhumeral Targeted Muscle Reinnervation
Authors: Chopan Mustafa , Spencer Nichols David , Chim Harvey
Published: August 2022

New developments in targeted muscle reinnervation promise better options for treatment of neuropathic pain and improved prosthetic control. For transhumeral amputations, the traditional approach involves an anterior incision to access the median and ulnar nerves and a second posterior incision to access the radial nerve. This is necessitated as exposure of motor branches of the radial nerve distal to the branch to the long head of the triceps is difficult from the anterior approach. Herein, we describe a technique for transferring the radial nerve proper distal to the long head branch to a motor branch to the medial or lateral head of the triceps through internal neurolysis and fascicular transfer. This allows all surgical steps to be performed through a single incision while preserving native motor branches to the biceps and triceps muscles.
Increasing angiotensin-converting enzyme 1 regulated by histone 3 lysine 27 hyperacetylation in high-fat diet-induced hypertensive rat kidney
Authors: Lin Ying , Li Ya-qi , Wang Hui , Wu Hao-jie , Bai Bao-ling , Ma Li-juan , Zou Ji-zhen , Zhang Qin , Shi Lin
Published: August 2022

Background:

Obesity is a key risk factor of hypertension. Angiotensin-converting enzyme 1 (ACE1) is a key enzyme involved in the renin–angiotensin–aldosterone system (RAAS), which contributes to obesity-related hypertension (OrHTN). Emerging evidence has shown that histone acetylation is also involved in OrHTN. As kidney is an effector organ that activates the RAAS by secreting renin after hypertension occurs, this study aimed to explore the regulatory role of histone acetylation on renal RAAS expression.

Methods:

Nineteen male Wistar rats were randomly divided into a control group (n = 9, fed normal chow) and a high-fat diet (HFD) group (n = 10, fed HFD for 16 weeks). The renal transcriptome and histone acetylation spectrum was analyzed by RNA sequencing and tandem mass spectrometry and was further confirmed by RT-qPCR, western blot, and immunohistochemistry. Then, chromatin immunoprecipitation (ChIP)-qPCR analysis was performed for the detection of DNA–protein interaction.

Results:

After 16-week HFD, the rats became obese with increased plasma triglyceride and high blood pressure. Increased ACE1 and histone 3 lysine 27 acetylation (H3K27ac) expression levels were found in OrHTN rat kidneys. The following ChIP-qPCR analysis illustrated that the upregulation of ACE1 transcription was mediated by increased H3K27ac.

Conclusion:

H3K27ac could be an important histone acetylation site that activates renal ACE1 in HFD-induced hypertensive rats.
Cyclooxygenase-2 is a critical determinant of angiotensin II-induced vascular remodeling and stiffness in resistance arteries of ouabain-treated rats
Authors: França-Neto Aldair de , Couto Gisele Kruger , Xavier Fabiano Elias , Rossoni Luciana Venturini
Published: August 2022

Objective:

To investigate the role of angiotensin II/AT1 receptor signaling and/or cyclooxygenase-2 (COX-2) activation on vascular remodeling and stiffening of the mesenteric resistance arteries (MRA) of ouabain-treated rats.

Methods:

Ouabain-treated (OUA, 30 μg kg/day for 5 weeks) and vehicle (VEH)-treated Wistar rats were co-treated with losartan (LOS, AT1R antagonist), nimesulide (NIM, COX-2 inhibitor) or hydralazine hydrochloride plus hydrochlorothiazide. MRA structure and mechanics were assessed with pressure myography and histology. Picrosirius red staining was used to determine the total collagen content. Western blotting was used to detect the expression of collagen I/III, MMP-2, Src, NFκB, Bax, Bcl-2 and COX-2. Reactive oxygen species (ROS) and plasma angiotensin II levels were measured by fluorescence and ELISA, respectively.

Results:

Blockade of AT1R or inhibition of COX-2 prevented ouabain-induced blood pressure elevation. Plasma angiotensin II level was higher in OUA than in VEH. LOS, but not hydralazine hydrochloride with hydrochlorothiazide, prevented inward hypotrophic remodeling, increased collagen deposition and stiffness, and oxidative stress in OUA MRA. LOS prevented the reduction in the total number of nuclei in the media layer and the Bcl-2 expression induced by OUA in MRA. The higher pSrc/Src ratio, NFκB/IκB ratio, and COX-2 expression in OUA MRA were also prevented by LOS. Likewise, COX-2 inhibition prevented vascular remodeling, mechanical changes, oxidative stress and inflammation in OUA MRA.

Conclusion:

The results suggest that, regardless of hemodynamic adjustments, the angiotensin II/AT1R/pSrc/ROS/NFκB/COX-2 pathway is involved in the development of MRA inward hypotrophic remodeling and stiffness in ouabain-treated rats.
COVID-19 Vaccination May Not Increase Rates of Corneal Graft Rejection
Authors: Busin Massimo , Zauli Giorgio , Pellegrini Marco , Virgili Gianni , Yu Angeli Christy
Published: August 2022

Purpose:

The aim of the study was to present the rates of rejection from 2018 to 2021 and evaluate the purported association between COVID-19 vaccination and corneal graft rejection.

Methods:

Cases of corneal graft rejection diagnosed between January 2018 and December 2021 were reviewed. The conditional Poisson regression model of the self-controlled case series method was used to estimate the incidence risk ratio of graft rejection after COVID-19 vaccination risk period compared with the control period. Based on outcomes of eyes that underwent keratoplasty from January 2018 to December 2020, Cox proportional hazard models were fitted with previous COVID-19 vaccination as a time-varying covariate.

Results:

Over the past 4 years, the annual tally of diagnosed cases of graft rejection (19 cases in year 2018, 19 cases in year 2019, 21 cases in year 2020, and 18 cases in year 2021) has remained relatively stable. Using the conditional Poisson regression analysis, no significant increase in the incidence rate of rejection in the risk period after COVID-19 vaccination was found (incidence risk ratio = 0.56, 95% confidence interval [CI] = 0.13–2.28, P = 0.70). Fitted as a time-varying covariate, previous COVID-19 vaccination was not associated with graft rejection in both unadjusted (hazard ratio =0.77, 95% CI = 0.29–5.46, P = 0.77) and adjusted Cox models (hazard ratio = 0.75, 95% CI = 0.10–5.52, P = 0.78).

Conclusions:

No notable increase in rates of corneal graft rejection was noted in year 2021 when COVID-19 vaccination was broadly implemented. The apparent temporal relationship between COVID vaccination and corneal graft rejection may not represent a causative association.
“Groove and Peel” Deep Anterior Lamellar Keratoplasty: How Deep Can You Go?
Authors: Son Hyeck-Soo , Rigi Mohammed , Srikumaran Divya , Eberhart Charles G. , Jun Albert S. , Soiberman Uri S.
Published: August 2022

Purpose:

The aim of the current research was to measure the thickness of the residual central corneal bed after performing the manual “Groove and Peel” deep anterior lamellar keratoplasty (GP-DALK) technique on human cadaveric eyes.

Methods:

The manual GP-DALK technique was performed on 6 human cadaver eyes by an experienced corneal surgeon. After surgery, the eye globes were fixed in 10% buffered formalin and embedded in paraffin. For each eye, 4-μm-thick hematoxylin and eosin sections involving the pupillary axis were obtained and examined. Using an image-processing software, 2 observers measured the corneal thickness of the residual central corneal bed and the peripheral corneal rims.

Results:

The overall mean central corneal bed thickness was 35.5 ± 12.9 μm, whereas the mean right and left peripheral rim thicknesses were 993.0 ± 141.1 and 989.3 ± 147.1 μm, respectively (P = 0.0006). In most corneas, the level of dissection reached almost to the pre-Descemetic collagen (Dua) layer.

Conclusions:

The GP-DALK technique is effective in removing most of the corneal stroma and may be non-inferior to “big-bubble” deep anterior lamellar keratoplasty in some cases.
Clinical and Microbiological Spectra and Therapeutic Outcomes of Polymicrobial Keratitis
Authors: Rathi Anubha , Ramazanova Khuraman , Murthy Somasheila I. , Mohamed Ashik , Joseph Joveeta , Doctor Mariya Bashir , Pandey Suchita , Rathi Varsha M.
Published: August 2022

Purpose:

The aim of this study was to evaluate the risk factors, microbiology, and treatment outcomes of polymicrobial keratitis (PMK).

Methods:

We retrospectively analyzed 65 patients diagnosed with PMK between 2016 and 2019. The clinical and microbiological characteristics and outcomes were evaluated. The primary outcome measure was clinical resolution of keratitis. Absolute success (group A) was defined as resolution of infection with medical treatment, qualified success (group B) was resolution with medical therapy and additional minor procedures, and failure (group C) was defined as worsening of infection and presence of corneal melting or perforation requiring therapeutic penetrating keratoplasty or evisceration.

Results:

Of 4764 cases of microbial keratitis, PMK was identified in 65 eyes of 65 patients (1.36%). Infiltrate was central in 60% (39 eyes). Predisposing factors were higher in group C and included uncontrolled diabetes mellitus in 25% (7/28), history of trauma/foreign body in 57.1% (16/28), and poor presenting visual acuity (0.9 for group A vs. 1.79 for group B vs. 3.00 logarithm of the minimum angle of resolution for group C; P = 0.02). Microbiological profiling revealed that a majority (95%: 62/65) had bacterial with fungal keratitis. High fluoroquinolone resistance was noted (57%; 34/59). Absolute success was achieved in 28.3% (17/60), qualified success in 16.6% (10/60), and treatment failure was noted in 55% (33/60). The final best corrected visual acuity in group A was significantly better than that in group B and C (0.44 vs. 3.00 vs. 2.78; P < 0.001).

Conclusions:

PMK is extremely rare but responds poorly to medical therapy. Bacterial with fungal etiology is predominant. Early surgical intervention to improve overall outcome is advocated.
Unbiased analysis of the dorsal root ganglion after peripheral nerve injury: no neuronal loss, no gliosis, but satellite glial cell plasticity
Authors: Schulte Annemarie , Lohner Hannah , Degenbeck Johannes , Segebarth Dennis , Rittner Heike L. , Blum Robert , Aue Annemarie
Published: August 2022

Pain syndromes are often accompanied by complex molecular and cellular changes in dorsal root ganglia (DRG). However, the evaluation of cellular plasticity in the DRG is often performed by heuristic manual analysis of a small number of representative microscopy image fields. In this study, we introduce a deep learning–based strategy for objective and unbiased analysis of neurons and satellite glial cells (SGCs) in the DRG. To validate the approach experimentally, we examined serial sections of the rat DRG after spared nerve injury (SNI) or sham surgery. Sections were stained for neurofilament, glial fibrillary acidic protein (GFAP), and glutamine synthetase (GS) and imaged using high-resolution large-field (tile) microscopy. After training of deep learning models on consensus information of different experts, thousands of image features in DRG sections were analyzed. We used known (GFAP upregulation), controversial (neuronal loss), and novel (SGC phenotype switch) changes to evaluate the method. In our data, the number of DRG neurons was similar 14 d after SNI vs sham. In GFAP-positive subareas, the percentage of neurons in proximity to GFAP-positive cells increased after SNI. In contrast, GS-positive signals, and the percentage of neurons in proximity to GS-positive SGCs decreased after SNI. Changes in GS and GFAP levels could be linked to specific DRG neuron subgroups of different size. Hence, we could not detect gliosis but plasticity changes in the SGC marker expression. Our objective analysis of DRG tissue after peripheral nerve injury shows cellular plasticity responses of SGCs in the whole DRG but neither injury-induced neuronal death nor gliosis.
Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors
Authors: Bansal Sandeep , Bechara Rabih I. , Patel Jiten D. , Mehta Hiren J. , Ferguson J. Scott , Witt Benjamin L. , Murgu Septimiu D. , Yasufuku Kazuhiro , Casal Roberto F.
Published: August 2022

Background:

Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors.

Methods:

Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study).

Results:

There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%.

Conclusion:

PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.
Endoscopic Endonasal Eustachian Tube Obliteration as a Treatment for Tension Pneumocephalus After Translabyrinthine Resection of Vestibular Schwannoma
Authors: Ji Keven S. Y. , Rimmer Ryan , Dogan Aclan , Cetas Justin S. , Ciporen Jeremy N. , Sanusi Olabisi , Gupta Sachin , Geltzeiler Mathew
Published: August 2022

Objective

Cerebrospinal fluid leak and pneumocephalus are rare but potentially devastating complications associated with translabyrinthine resection of cerebellopontine angle masses. Persistent pneumocephalus despite proximal eustachian tube (ET) obliteration is rare. We describe, to our knowledge, the first report of successful management of tension pneumocephalus by endoscopic endonasal ET obliteration using a novel V-loc (Covidien; Medtronic, Minneapolis, MN) suture technique.

Patients

A 63-year-old man presented with altered mental status 10 months after translabyrinthine excision of a left cerebellopontine angle vestibular schwannoma measuring 2.8 × 2.9 × 3.3 cm. Computed tomography demonstrated diffuse ventriculomegaly and new pneumocephalus along the right frontal lobe, lateral ventricles, and third ventricle, and air within the left translabyrinthine resection cavity.

Intervention

The patient underwent left-sided endoscopic endonasal ET obliteration using 2-0, 9-inch V-loc suture.

Main Outcome Measure

Postoperatively, the patient's mental status improved with a decrease in size of the lateral and third ventricles on computed tomography.

Conclusion

Endoscopic endonasal ET obliteration, a technique previously applied to recalcitrant cerebrospinal fluid leaks, is a safe and reasonable alternative to reentering the original surgical site for patients with pneumocephalus after lateral skull base surgery. Utilizing a V-loc suture for this technique instead of a traditional suture may improve procedural ease and speed.
Frailty Is Superior to Age for Predicting Readmission, Prolonged Length of Stay, and Wound Infection in Elective Otology Procedures
Authors: Stidham Katrina , Naftchi Alexandria F. , Spirollari Eris , Vaserman Grigori , Vazquez Sima , Das Ankita , Colasacco Christine , Culbertson Sara , Ng Christina , Graifman Gillian , Beaudreault Cameron , Lui Aiden K. , Dominguez Jose F. , Kazim Syed Faraz , Schmidt Meic , Bowers Christian A.
Published: August 2022

Objective

To determine the predictive ability of the 5-point modified frailty index relative to age in elective otology patients.

Study Design

Retrospective database analysis.

Setting

Multicenter, national database of surgical patients.

Patients

We selected all elective surgical patients who received tympanoplasty, tympanomastoidectomy, mastoidectomy, revision mastoidectomy, and cochlear implant procedures from 2016 to 2019 from the National Surgical Quality Improvement database.

Interventions

Therapeutic.

Main Outcome Measures

Readmission rates, discharge disposition, reoperation rates, and extended length of hospital stay.

Results

Utilizing receiver operating characteristics with area under the curve (AUC) analysis, nonrobust status was determined to be a superior predictor relative to age of readmission (AUC = 0.628 [p < 0.001] versus AUC = 0.567 [p = 0.047], respectively) and open wound infection relative to age (AUC = 0.636 [p = 0.024] versus AUC = 0.619 [p = 0.048], respectively). Nonrobust otology patients were more likely to have dyspnea at rest and an American Society of Anesthesiology score higher than 2 before surgery (odds ratios, 13.304 [95% confidence interval, 2.947–60.056; p < 0.001] and 7.841 [95% confidence interval, 7.064–8.704; p < 0.001], respectively).

Conclusion

Nonrobust status was found to be a useful predictor of readmission and prolonged length of stay in patients undergoing elective otology procedures, which generally have low complication rate. Given the aging population and corresponding increase in otology disease, it is important to use age-independent risk stratification measures. Frailty may provide a useful risk stratification tool to select surgical candidates within the aging population.
Etiologies of Proctitis at a Sexual Health Clinic in Seattle, Washington From 2011 to 2021
Authors: Kumbhakar Raaka , Barbee Lindley A. , Berzkalns Anna , Herrmann Susannah , Ramchandani Meena S. , Golden Matthew R. , Dombrowski Julia C.
Published: August 2022

We analyzed microbiologic etiologies of proctitis among patients seen in an urban sexual health clinic during 2011 to 2021. Among 759 cases, 179 (24%) tested positive for Neisseria gonorrhoeae, 171 (23%) for Chlamydia trachomatis, 21 (3%) for herpes simplex virus, 30 (4%) for syphilis, and 73 (10%) for multiple pathogens; no pathogen was identified in 425 (56%).
Intermediate Outcomes of Orbital Wall Reconstruction Using Different Alloplastic Materials: Which Is Ideal?
Authors: Kohyama Keishi , Ishihara Takuma , Tsuboi Yoshiki , Morishima Yoko
Published: August 2022

Background:

Despite the popularity and superiority of resorbable alloplastic materials in orbital fracture reconstruction, it is unclear whether the reconstructed wall is maintained after implant resorption. Although unsintered hydroxyapatite/poly-L-lactide (u-HA/PLLA) is one such material, it is different from conventional materials for the replacement of natural bones. Therefore, this study investigated the intermediate-term safety and efficacy of u-HA/PLLA implants compared to those of implants made with other alloplastic materials.

Methods:

We retrospectively analyzed 240 eligible patients who underwent orbital fracture reconstruction with one alloplastic material between January 2006 and October 2018. Materials used for treatment were as follows: u-HA/PLLA sheet in 101 patients; u-HA/PLLA mesh in 38 patients; poly-L-lactic acid (PLA)/poly-glycolic acid (PGA) mesh in 47 patients; silicone sheet in 35 patients; and titanium mesh in 19 patients. Intermediate-term follow-up was performed for a median duration of 48.2 months. A chart review was performed. Postoperative complications and factors affecting them were studied. Reconstructed area deformities were assessed using computed tomography.

Results:

Postoperative complications occurred significantly more frequently in patients reconstructed with the silicone sheet than in those reconstructed with the u-HA/PLLA sheet. Deformities were found for the silicone sheet (28.6%) and PLA/PGA mesh (31.9%). These deformity rates were significantly higher than those for the u-HA/PLLA sheet.

Conclusions:

Compared to other alloplastic materials, u-HA/PLLA has low rates of postoperative complications and reconstructed area deformities. Because of its complete absorption, clinicians should consider using u-HA/PLLA as an alloplastic material for orbital wall reconstruction.
Higher Soluble CD163 in Blood Is Associated With Significant Depression Symptoms in Men With HIV
Authors: Anderson Albert M. , Bhondoekhan Fiona , Curanovic Dusica , Connelly Margery A. , Otvos James D. , Post Wendy S. , Michos Erin D. , Stosor Valentina , Levine Andrew , Seaberg Eric , Weinstein Andrea M. , Becker James T.
Published: August 2022

Background:

People with HIV (PWH) are more likely to experience depression, a highly morbid disease. More evidence is needed to better understand mechanisms of depression in PWH. We evaluated a panel of blood biomarkers in relation to depression symptoms in the Multicenter AIDS Cohort Study (MACS).

Setting:

Four sites in the United States.

Methods:

A cross-sectional analysis was performed within the MACS, a prospective study of cisgender men with and without HIV. Depression was assessed with the Center for Epidemiological Studies-Depression Scale, and six blood biomarkers were measured: GlycA, high sensitivity C-reactive protein (CRP), interleukin-6, CCL2, soluble CD14 (sCD14), and soluble CD163 (sCD163). Using univariable and multivariable logistic regression, the biomarkers and other factors were evaluated in relation to significant depression symptoms (SDS) by Center for Epidemiological Studies-Depression score ≥16.

Results:

784 men were analyzed; most of whom (63%) were PWH. PWH were more likely to have SDS (32% vs. 21%). In univariable analysis, higher GlycA, CRP, and sCD163 concentrations were associated with SDS. In multivariable analysis, however, only higher sCD163 concentration was associated with SDS (odds ratio = 2.30, 95% CI = 1.11 to 4.76). This relationship was driven by the PWH group (odds ratio = 2.72, 95% CI = 1.12 to 6.58) and remained significant when controlling for antidepressant use. Lack of college education was also associated with SDS.

Conclusions:

Higher sCD163, a marker of macrophage activation, was significantly associated with significant depression symptoms in the MACS. Further research on this biomarker and macrophage activation in general is warranted to better understand and treat depression in PWH.
Economic Well-being and Associated Mediating Pathways to Improved Antiretroviral Therapy Adherence Among Adolescents Living With HIV: A Prospective Cohort Study in South Africa
Authors: Steinert Janina Isabel , Shenderovich Yulia , Smith Michael , Zhou Siyanai , Toska Elona , Cluver Lucie
Published: August 2022

Background:

Adolescents living with HIV exhibit lower levels of adherence to antiretroviral therapy (ART) than other age groups. Poverty is a key barrier to ART adherence. This study aims at understanding how alleviating poverty through structural and internal pathways can help increase ART adherence among adolescents.

Setting:

Eastern Cape province, South Africa.

Methods:

One thousand forty-six adolescents living with HIV were recruited from 53 public health care facilities and interviewed at 3 data collection waves with a retention rate of 89% and a mortality rate of 3%. Data were collected by face-to-face, device-assisted interviews. Hybrid probit regressions and a structural equation path analysis were used to estimate the association between poverty reduction (increased access to basic necessities) and the pathways by which it could improve ART adherence.

Results:

Self-reported ART adherence ranged from an average of 66% (n = 615) at baseline to 75% (n = 700) in the last wave. Within-person and between-person improvements in economic well-being were associated with significant increases in adolescent ART adherence. On average, adolescents with access to 3 additional basic needs experienced a 4 percentage-point increase in the probability of ART adherence. Structural pathways to improved ART adherence included participants having enough money to travel to the clinic and sufficient food to eat when taking medication. Internal pathways included improved psychological well-being and reduced internalized HIV stigma.

Conclusion:

Poverty reduction programs such as HIV-sensitive social protection can address structural and psychological pathways to increase ART adherence among economically disadvantaged adolescents by incentivizing demand-side interventions and the provision of quality essential services.
Dynamics of Total and Intact HIV-1 DNA in Virologically Suppressed Patients Switching to DTG-Based or ATV-Based Dual Therapy
Authors: Dragoni Filippo , Rossetti Barbara , Lombardi Francesca , Spertilli Raffaelli Chiara , Bartolini Niccolò , Giammarino Federica , Moschese Davide , Di Giambenedetto Simona , Fabbiani Massimiliano , De Luca Andrea , Vicenti Ilaria , Zazzi Maurizio , Saladini Francesco
Published: August 2022

Background:

Clinical trials have demonstrated noninferior viral suppression rates of selected 2-drug regimens (2DRs) over standard 3-drug regimens (3DRs). However, the effect of simplification to 2DRs on HIV-1 reservoir remains to be fully assessed.

Setting:

Retrospective analyses of samples of virologically suppressed people living with HIV remaining on the same 3DRs or switching to DTG + 3TC or ATV/r + 3TC 2DRs.

Methods:

Whole blood samples were collected at enrollment and after 48 weeks. Total HIV-1 DNA (tDNA) and intact HIV-1 DNA (iDNA) were quantified by droplet digital polymerase chain reaction and intact proviral DNA assay, respectively. Statistical analysis was performed to identify associations among variables, and multiple linear regression was used to analyze potential predictors of tDNA and iDNA changes over time.

Results:

Forty-seven individuals were switched to DTG + 3TC 2DR (N = 23) and ATV/r + 3TC 2DR (N = 24), while 18 remained on 3DRs. tDNA did not change either in the overall population or in the 3DR and 2DR groups. iDNA decreased significantly in the whole data set and in the overall 3DR and 2DR groups (P = 0.001, P = 0.039 and P = 0.009, respectively). iDNA, but not tDNA, was inversely correlated with the time of viral suppression (P = 0.002) and time under antiretroviral therapy (P = 0.006). Higher nadir CD4+ T-cell counts (P = 0.001) and lower zenith viral load (P = 0.02) showed an association with the decrease of iDNA, but not with tDNA.

Conclusions:

Both tDNA and iDNA dynamics supported noninferior efficacy of 2DRs over 3DRs. iDNA could be more informative than tDNA in analyzing the dynamics of the HIV-1 reservoir under different treatment strategies.
Refractory Giardiasis in a Child with Steroid Resistant Nephrotic Syndrome
Authors: Kalita Jitu Mani , Sharma Kirtika , Mohammad Naila , Tak Vibhor , Mittal Aliza , Nag Vijaya Lakshmi
Published: August 2022

Giardiasis is an infection of the small intestine caused by the protozoan parasite Giardia intestinalis and one of the most common parasitic intestinal diseases in humans worldwide. It mainly manifests as a self-limited illness in case of immunocompetent patients and don’t usually require any treatment. However, immunodeficiency is a risk factor for the onset of severe Giardia infection. In this report, a case of recurrent giardiasis refractory to nitroimidazole therapy is presented. A 7-year-old male patient with steroid resistant nephrotic syndrome came to our hospital because of chronic diarrhoea. Patient was on immunosuppressive therapy for long duration. Microscopic examination of stool showed a significant number of trophozoites and cysts of Giardia intestinalis . Treatment with metronidazole for longer duration than recommended has failed to clear the parasite in the present case.
Bright light therapy and early morning attention, mathematical performance, electroencephalography and brain connectivity in adolescents with morning sleepiness
Authors: Teicher Martin H. , Bolger Elizabeth , Hernandez Garcia Laura C. , Hafezi Poopak , Weiser Leslie P. , McGreenery Cynthia E. , Khan Alaptagin , Ohashi Kyoko
Published: August 2022

Adolescents typically sleep too little and feel drowsy during morning classes. We assessed whether early morning use of an LED bright light device could increase alertness in school students. Twenty-six (8M/18F) healthy, unmedicated participants, ages 13-18 years, (mean 17.1±1.4) were recruited following screenings to exclude psychopathology. Baseline assessments were made of actigraph-assessed sleep, attention, math solving ability, electroencephalography and structural and functional MRI (N=10-11, pre-post). Participants nonrandomly received 3-4 weeks of bright light therapy (LiteBook Edge™) for 30 minutes each morning and used blue light blocking glasses for 2 hours before bedtime. LiteBooks™ were modified to surreptitiously record degree of use so that the hypothesis tested was whether there was a significant relationship between degree of use and outcome. LiteBooks™ were used 57±18% (range 23%–90%) of recommended time. There was a significant association between degree of use and: (1) increased beta spectral power in frontal EEG leads (primary measure); (2) greater post-test improvement in math performance and reduction in errors of omission on attention test; (3) earlier rise times on non-school days and reduced day-to-day variability in rise times; (4) increased dentate gyrus volume and (5) enhanced frontal connectivity with temporal, occipital and cerebellar regions during Go/No-Go task performance. Degree of bright light therapy use was associated with improvement in sleep cycle consistency, arousal, attention and functional connectivity, but not sleep onset or duration (primary measures). Although this was an open study, it suggests that use of bright morning light and blue light blocking glasses before bed may benefit adolescents experiencing daytime sleepiness.
Astrocytes in the retinorecipient superior colliculus display unique cellular and structural properties
Authors: Visser Josien , Ribot Jérôme , Pauletti Alberto , Mazaud David , Henneberger Christian , Rouach Nathalie
Published: August 2022

Astrocytes have long been considered to be a largely homogeneous cell population. Recent studies however suggest that astrocytes are highly adapted to the local neuronal circuitry. Glucose utilization in the retinorecipient superior colliculus (SC) is one of the highest in the brain. Since metabolic support to neurons is a major function of astrocytes, they could be of particular relevance in this region and display specific features. However, little is known about astrocytes and their interactions with neurons in this multisensory brain area. We thus here investigated region-specific cellular and structural properties of astrocytes in the visual layer of the SC. Using morphological reconstructions, fluorescent recovery after photobleaching (FRAP) and superresolution imaging, we found that astrocytes from the visual layers of the SC are highly distinct with a higher cellular density, a more complex morphology and a stronger proximity to synapses compared to astrocytes from the primary visual cortex and the hippocampus. These data point to astroglial diversity and specialization within neural circuits integrating sensory information in the adult brain.
Beyond Linear Neural Envelope Tracking: A Mutual Information Approach
Authors: De Clercq Pieter , Vanthornhout Jonas , Vandermosten Maaike , Francart Tom
Published: August 2022

The human brain tracks the temporal envelope of speech, which contains essential cues for speech understanding. Linear models are the most common tool to study neural envelope tracking. However, information on how speech is processed can be lost since nonlinear relations are precluded. As an alternative, mutual information (MI) analysis can detect both linear and nonlinear relations. Yet, several different approaches to calculating MI are applied without consensus on which approach to use. Furthermore, the added value of nonlinear techniques remains a subject of debate in the field. To resolve this, we applied linear and MI analyses to electroencephalography (EEG) data of participants listening to continuous speech. Comparing the different MI approaches, we conclude that results are most reliable and robust using the Gaussian copula approach, which first transforms the data to standard Gaussians. With this approach, the MI analysis is a valid technique for studying neural envelope tracking. Like linear models, it allows spatial and temporal interpretations of speech processing, peak latency analyses, and applications to multiple EEG channels combined. Finally, we demonstrate that the MI analysis can detect nonlinear components on the single-subject level, beyond the limits of linear models. We conclude that the MI analysis is a more informative tool for studying neural envelope tracking.

Significance statement

In the present study, we addressed key methodological considerations for MI applications. Traditional MI methodologies require the estimation of a probability distribution at first. We show that this step can introduce a bias in the results and, consequently, severely impact interpretations. As an alternative, we propose using the parametric Gaussian copula method, which we demonstrated to be robust against biases. Second, using the parametric MI analysis, we show that there is nonlinear variance in the EEG data that the envelope of speech can explain at the single-subject level, proving its added value to neural envelope tracking. We conclude that the MI analysis is a statistically more powerful tool for studying neural envelope tracking than linear models. In addition, it retains spatial and temporal characteristics of speech processing which are lost when using more complex deep neural networks.
Modulation of spinal circuits following phase-dependent electrical stimulation of afferent pathways
Authors: Pascual-Valdunciel Alejandro , Kurukuti Nish Mohith , Montero-Pardo Cristina , Barroso Filipe Oliveira , Pons José Luis
Published: August 2022

Peripheral electrical stimulation (PES) of afferent pathways is a tool commonly used to induce neural adaptations in some neural disorders such as pathological tremor or stroke. However, the neuromodulatory effects of stimulation interventions synchronized with physiological activity (closed-loop strategies) have been scarcely researched in the upper-limb. Here, the short-term spinal effects of a 20-minute stimulation of afferent pathways protocol applied with a closed-loop strategy named Selective and Adaptive Timely Stimulation (SATS) was explored. The SATS strategy was applied to the radial nerve in-phase (INP) or out-of-phase (OOP) with respect to the muscle activity of the extensor carpi radialis (ECR). The neural adaptations at the spinal cord level were assessed for the flexor carpi radialis (FCR) by measuring disynaptic Group I inhibition, Ia presynaptic inhibition, and Ib facilitation from the H-reflex, and estimation of the neural drive before, immediately after, and 30 minutes after the intervention. SATS strategy was proved to deliver synchronous stimulation with the real-time measured muscle activity with an average delay of 17±8 ms. SATS-INP induced an increase of the disynaptic Group I inhibition (77±23 % of baseline conditioned FCR H-reflex), while SATS-OOP elicited the opposite effect (125±46 %). Not all the subjects maintained the changes after 30 minutes. Additionally, no other significant specific neural adaptations were found for the rest of measurements. These results suggest that the short-term modulatory effects of phase-dependent PES occur at the specific targeted spinal pathways for the wrist muscles in healthy individuals. Overall, timely recruitment of afferent pathways with the muscle activity is a fundamental principle which should be considered in tailoring PES protocols for the specific neural circuits to be modulated.
Bayesian Tests for Random Mating in Polyploids
Authors: Gerard David
Published: August 2022

Hardy-Weinberg proportions (HWP) are often explored to evaluate the assumption of random mating. However, in autopolyploids, organisms with more than two sets of homologous chromosomes, HWP and random mating are different hypotheses that require different statistical testing approaches. Currently, the only available methods to test for random mating in autopolyploids (i) heavily rely on asymptotic approximations and (ii) assume genotypes are known, ignoring genotype uncertainty. Furthermore, these approaches are all frequentist, and so do not carry the benefits of Bayesian analysis, including ease of interpretability, incorporation of prior information, and consistency under the null. Here, we present Bayesian approaches to test for random mating, bringing the benefits of Bayesian analysis to this problem. Our Bayesian methods also (i) do not rely on asymptotic approximations, being appropriate for small sample sizes, and (ii) optionally account for genotype uncertainty via genotype likelihoods. We validate our methods in simulations, and demonstrate on two real datasets how testing for random mating is more useful for detecting genotyping errors than testing for HWP (in a natural population) and testing for Mendelian segregation (in an experimental S1 population). Our methods are implemented in Version 2.0.2 of the hwep R package on the Comprehensive R Archive Networkhttps://cran.r-project.org/package=hwep.
Aldy 4: An efficient genotyper and star-allele caller for pharmacogenomics
Authors: Hari Ananth , Zhou Qinghui , Gonzaludo Nina , Harting John , Scott Stuart A. , Sahinalp S. Cenk , Numanagić Ibrahim
Published: August 2022

High-throughput sequencing provides sufficient means for determining genotypes of clinically important pharmacogenes that can be used to tailor medical decisions to individual patients. However, pharmacogene genotyping, also known as star-allele calling, is a challenging problem that requires accurate copy number calling, structural variation discovery, variant calling and phasing within each pharmacogene copy present in the sample.

Here we introduce Aldy 4, a fast and efficient tool for genotyping pharmacogenes that utilizes combinatorial optimization for accurate star-allele calling across different sequencing technologies. Aldy 4 adds support for long reads and ships with a novel phasing model and improved copy number and variant calling models.

We compare Aldy 4 against the current state-of-the-art star-allele callers on a large and diverse set of samples and genes sequenced by various sequencing technologies, such as whole-genome and targeted Illumina sequencing, barcoded 10X Genomics and PacBio HiFi. We show that Aldy 4 is the most accurate star-allele caller with near-perfect accuracy in all evaluated contexts. We hope that Aldy remains an invaluable tool in the clinical toolbox even with the advent of long-read sequencing technologies.

Availability

Aldy 4 is available at https://github.com/0xTCG/aldy.
The addiction-susceptibility TaqIA/Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) controls reward and metabolism through dopamine receptor type 2 (DR2)-expressing neurons
Authors: Montalban Enrica , Walle Roman , Castel Julien , Ansoult Anthony , Hassouna Rim , Foppen Ewout , Fang Xi , Hutelin Zach , Mickus Sophie , Perszyk Emily , Petitbon Anna , Berthelet Jérémy , Rodrigues-Lima Fernando , Cebrian-Serrano Alberto , Gangarossa Giuseppe , Martin Claire , Trifilieff Pierre , Bosch-Bouju Clémentine , Small Dana. M , Luquet Serge
Published: August 2022

Significant evidence highlights the importance of genetic variants in the development of psychiatric and metabolic conditions. Among these, the Taq1A polymorphism is one of the most commonly studied in psychiatry. TaqIA is located in the gene that codes for the Ankyrin repeat and kinase domain containing 1 kinase (ANKK1) near the dopamine D2 dopamine receptor (DR2) gene. Depending on race it affects 30 to 80% of the population and its homozygous expression of the A1 allele correlates with a 30 to 40% reduction of striatal DR2, a typical feature of addiction, over-eating and other psychiatric pathologies. The mechanisms by which the variant influences dopamine signaling and behavior is unknown. Here we used transgenic and viral-mediated strategies to reveal the role of ANKK1 in the regulation of activity and functions of the striatum. We found that Ankk1 is preferentially enriched in striatal DR2 expressing neurons and that Ankk1 loss-of-function in dorsal and ventral striatum leads to alteration in learning, impulsive, and flexible behaviors resembling the endophenotypes described in A1 carriers. We also observed an unsuspected role of ANKK1 in striatal DR2-expressing neurons in the ventral striatum in the regulation of energy homeostasis and documented differential nutrient partitioning in humans with versus without the A1 allele. Overall, our data demonstrate that the Ankk1 gene is necessary for the integrity of striatal functions and reveal a new role for ANKK1 in the regulation of body metabolism.
Egocentric Bias in Effort Comparison Tasks Is Driven by Sensory Asymmetries, Not Attribution Bias
Authors: Stinson Caedyn , Kagan Igor , Pooresmaeili Arezoo
Published: August 2022

When comparing themselves with others, people often perceive their own actions and behaviour favourably. This phenomenon is often categorised as a bias of attribution, with favourable self-evaluation resulting from differing explanations of one’s own behaviour and that of others. However, studies on availability biases offer an alternative explanation, ascribing egocentric biases to the inherent sensory asymmetries between performing an action and merely observing it. In this study, we used a paradigm that allowed us to directly compare these two distinct sources of bias. Participants perceived the tasks they performed to be harder than the tasks they observed, but demonstrated no bias driven by favourable self-evaluation. Furthermore, the degree of overestimation of the difficulty of performed tasks was magnified as overall task difficulty increased. These findings suggest that egocentric biases are in part derived from sensory asymmetries inherent to the first-person perspective.
rRNA depletion for holobiont metatranscriptome profiling across demosponges
Authors: Vargas Sergio , Rivera-Vicéns Ramón E. , Eitel Michael , Leiva Laura , Büttner Gabrielle , Wörheide Gert
Published: August 2022

Despite the extensive knowledge of sponge microbiome diversity, a critical knowledge gap persists concerning the molecular mechanisms that govern host-symbiont interactions. Deciphering these mechanisms is crucial for understanding how sponge holobionts respond to environmental changes and identifying potential disruptions in sponge-microbe associations. A hindrance to progress in characterizing these molecular crosstalk mechanisms is the scarcity of broadly applicable molecular methods for efficiently sequencing meta-transcriptomes across a diverse array of sponge species. To tackle this challenge, we have introduced a hybrid-capture strategy capable of selectively depleting sponge and bacterial rRNA from total RNA extracts obtained from highly divergent demosponges with varying microbiome complexities. Our innovative pan-demosponge rRNA depletion approach streamlines the efficient characterization of metatranscriptomes within diverse demosponge holobionts, concurrently facilitating the quantification of gene expression in both the host and its microbiome. This methodological advancement represents a significant stride in unraveling the molecular intricacies of sponge-microbe interactions, providing a robust platform for future investigations across a broad spectrum of sponge species.
Multi-sugar fermentation of lignocellulosic hydrolysate under industrially relevant conditions: comparison of several yeast strains
Authors: Froehlich Allan , Covalla Sean , Fromanger Romain , Hämäläinen Joonas , Kaartinen Tarja , Mastel Beth , Laine M. Minna
Published: August 2022

Both hexose- and pentose-fermenting yeasts are commercially available. The aim of this study was to test several yeast strains for their ability to ferment lignocellulosic feedstock and to evaluate their usability in a bioethanol production process based on the Cellunolix® concept. The Cellunolix® bioethanol demonstration plant of St1 uses sawdust to produce second-generation lignocellulosic ethanol. The study was performed in collaboration with yeast providers using two types of pretreated and filtered lignocellulosic ethanol hydrolysate originating from pine and willow. Ten pentose- and three hexose-fermenting yeast strains were tested. They all performed well under industrial conditions but differed in the rate of detoxification and profile for utilization of different sugars. A satisfactory 82–97% fermentation yield of a multi-sugar hydrolysate containing glucose, mannose, galactose, arabinose and xylose was achieved within 48 h. The results indicate significant potential for the usability of pentose-fermenting strains with real industrial hydrolysates and settings.
Zebrafish Slit2 and Slit3 act together to regulate retinal axon crossing at the midline
Authors: Davison Camila , Bedó Gabriela , Zolessi Flavio R.
Published: August 2022

Slit-Robo signaling regulates midline crossing of commissural axons in different systems. In the zebrafish, all retinofugal axons cross at the optic chiasm to innervate the contralateral tectum. Here, the mutant for the Robo2 receptor presents severe axon guidance defects, which were not completely reproduced in a Slit2 ligand null mutant. Since slit3 is also expressed around this area at the stage of axon crossing, we decided to analyze the possibility that it collaborates with Slit2 in this process. We found that the disruption of slit3 expression by sgRNA-Cas9 injection caused similar, albeit slightly milder, defects than those of the slit2 mutant, while the same treatment in the slit2-/- background caused much more severe defects, comparable to those observed in robo2 mutants. Tracking analysis of in vivo time-lapse experiments indicated differential but complementary functions of these secreted factors in the correction of axon turn errors around the optic chiasm. Interestingly, RT-qPCR analysis showed a mild increase in slit2 expression in slit3 deficient embryos, but not the opposite. Our observations support the previously proposed “repulsive channel” model for Slit-Robo action at the optic chiasm, with both Slits acting in different manners, most probably relating to their different spatial expression patterns.