bluuebunny/crossref_metadata_2025 huggingface dataset:
Histologic Classification and Molecular Signature of Polymorphous Adenocarcinoma (PAC) and Cribriform Adenocarcinoma of Salivary Gland (CASG)
Authors: Xu Bin , Barbieri Andrea L. , Bishop Justin A. , Chiosea Simon I. , Dogan Snjezana , Di Palma Silvana , Faquin William C. , Ghossein Ronald , Hyrcza Martin , Jo Vickie Y. , Lewis James S. , Lozada John R. , Michal Michal , Pareja Fresia G. , Perez-Ordonez Bayardo , Prasad Manju L. , Purgina Bibianna , Reis-Filho Jorge S. , Scognamiglio Theresa , Sebastiao Ana P.M. , Seethala Raja R. , Skálová Alena , Smith Stephen M. , Tekkeşin Merva S. , Thompson Lester D.R. , Wasseman Jason K. , Wenig Bruce M. , Weinreb Ilan , Katabi Nora
Published: January 2020

Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominantly cribriform and solid patterns with glomeruloid structures and optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or a variant of PAC. We aimed to assess the level of agreement among 25 expert Head and Neck pathologists in classifying these tumors. Digital slides of 48 cases were reviewed and classified as: PAC, CASG, tumors with ≥50% of papillary architecture (PAP), and tumors with indeterminate features (IND). The consensus diagnoses were correlated with a previously reported molecular alteration. The consensus diagnoses were PAC in 18/48, CASG in16/48, PAP in 3/48, and IND in 11/48. There was a fair interobserver agreement in classifying the tumors (κ=0.370). The full consensus was achieved in 3 (6%) cases, all of which were classified as PAC. A moderate agreement was reached for PAC (κ=0.504) and PAP (κ=0.561), and a fair agreement was reached for CASG (κ=0.390). IND had only slight diagnostic concordance (κ=0.091). PAC predominantly harbored PRKD1 hotspot mutation, whereas CASG was associated with fusion involving PRKD1, PRKD2, or PRKD3. However, such molecular events were not exclusive as 7% of PAC had fusion and 13% of CASG had mutation. In conclusion, a fair to moderate interobserver agreement can be achieved in classifying PAC and CASG. However, a subset (23%) showed indeterminate features and was difficult to place along the morphologic spectrum of PAC/CASG among expert pathologists. This may explain the controversy in classifying these tumors.
Validity Analysis on the Findings of Dehydration in 2 to 24-Month-Old Children With Acute Diarrhea
Authors: Vatandas Nilgun Salk , Yurdakok Kadriye , Yalcin Siddika Songul , Celik Melda
Published: January 2020

Objective

The most common cause of diarrheal mortality in children is dehydration. In this study, we aimed to assess the validity (sensitivity and specificity) of history and the clinical and laboratory findings in in the diagnosis of dehydration in children younger than 2 years with acute diarrhea.

Methods

One hundred twenty-six 2 to 24-month-old children with acute diarrhea, who were admitted to Hacettepe University Ihsan Dogramaci Children's Hospital's Diarrheal Diseases Treatment and Training Unit, were included. The patients were examined on admission for clinical findings of dehydration. Percent weight loss on admission was calculated by using the weight on admission and the weight after the diarrhea resolution and was used as the golden standard for analyzing the validity of clinical and laboratory findings.

Results

Compared with the golden standard, dehydration was overestimated in 13% of the cases and underestimated in 7% when using only the World Health Organization criteria. Dehydrated children had higher diarrheal frequency and longer anuria time. Thirst, weakness, sunken fontanelle, sunken eyes, decreased tears, dry mucous membranes, and dry lip were detected in children with 2% or greater of weight loss. The most valid laboratory findings were low serum pH (<7.30), low bicarbonate (<15 mmol/L), and hyperurisemia (>5.8 mg/dL). In multivariate analysis, physical findings, such as thirst, dry mucous membranes, weakness, sunken eyes, hoarse crying, and low pH, were found to be significant for the diagnosis of dehydration.

Conclusions

In children with acute diarrhea, diarrheal frequency and last urination time should be asked, thirst, dry mucous membranes, weakness, sunken eyes, and hoarse crying should be examined.
Persistent genital arousal disorder: a special sense neuropathy
Authors: Oaklander Anne Louise , Sharma Saurabh , Kessler Katie , Price Bruce H.
Published: January 2020

Introduction:

Persistent genital arousal (PGAD) is a syndrome of unprovoked sexual arousal/orgasm of uncertain cause primarily reported in female patients. Most patients are referred for mental-health treatment, but as research suggests associations with neurological symptoms and conditions, there is need to analyze cases comprehensively evaluated by neurologists.

Methods:

The IRB waived consent requirements for this retrospective university-hospital study. We extracted and analyzed neurological symptoms, test, and treatment results from all qualifying participants' records and recontacted some for details.

Results:

All 10 participants were female; their PGAD symptoms began between ages 11 to 70 years. Two patterns emerged: 80% reported daily out-of-context sexual arousal episodes (≤30/day) that usually included orgasm and 40% reported lesser, often longer-lasting, nonorgasmic arousals. Most also had symptoms consistent with sacral neuropathy—70% had urologic complaints and 60% had neuropathic perineal or buttock pain. In 90% of patients, diagnostic testing identified anatomically appropriate and plausibly causal neurological lesions. Sacral dorsal-root Tarlov cysts were most common (in 4), then sensory polyneuropathy (2). One had spina bifida occulta and another drug-withdrawal effect as apparently causal; lumbosacral disc herniation was suspected in another. Neurological treatments cured or significantly improved PGAD symptoms in 4/5 patients, including 2 cures.

Conclusions:

Although limited by small size and referral bias to neurologists, this series strengthens associations with Tarlov cysts and sensory polyneuropathy and suggests new ones. We hypothesize that many cases of PGAD are caused by unprovoked firing of C-fibers in the regional special sensory neurons that subserve sexual arousal. Some PGAD symptoms may share pathophysiologic mechanisms with neuropathic pain and itch.
HIV Preexposure Prophylaxis Cascades to Assess Implementation in Australia: Results From Repeated, National Behavioral Surveillance of Gay and Bisexual Men, 2014–2018
Authors: Holt Martin , Lee Evelyn , Lea Toby , Bavinton Benjamin , Broady Tim , Mao Limin , MacGibbon James , Keen Phillip , Murphy Dean , Bear Brandon , Crawford David , Ellard Jeanne , Kolstee Johann , Power Cherie , Prestage Garrett , Grulich Andrew , Guy Rebecca , de Wit John
Published: January 2020

Background:

HIV prevention cascades can assist in monitoring the implementation of prevention methods like preexposure prophylaxis (PrEP). We developed 2 PrEP cascades for Australia's primary HIV-affected population, gay and bisexual men.

Methods:

Data were drawn from 2 national, repeated, cross-sectional surveys (the Gay Community Periodic Surveys and PrEPARE Project). One cascade had 3 steps, and the other had 7 steps. Trends over time were assessed using logistic regression. For the most recent year, we identified the biggest drop between steps in each cascade and compared the characteristics of men between the 2 steps using multivariate logistic regression.

Results:

Thirty-nine thousand six hundred and seventy non–HIV-positive men participated in the Periodic Surveys during 2014–2018. PrEP eligibility increased from 28.1% (1901/6762) in 2014 to 37.3% (2935/7878) in 2018 (P < 0.001), awareness increased from 29.6% (563/1901) to 87.1% (2555/2935; P < 0.001), and PrEP use increased from 3.7% (21/563) to 45.2% (1155/2555; P < 0.001). Of 1038 non–HIV-positive men in the PrEPARE Project in 2017, 54.2% (n = 563) were eligible for PrEP, 97.2% (547/563) were aware, 67.6% (370/547) were willing to use PrEP, 73.5% (272/370) had discussed PrEP with a doctor, 78.3% (213/272) were using PrEP, 97.2% (207/213) had recently tested, and 75.8% (157/207) reported reduced HIV concern and increased pleasure because of PrEP. The break point analyses indicated that PrEP coverage was affected by geographical availability, education level, employment, and willingness to use PrEP.

Conclusions:

PrEP eligibility, awareness, and use have rapidly increased among Australian gay and bisexual men. The cascades identify disparities in uptake by eligible men as a result of socioeconomic factors and PrEP's acceptability.
Pattern and Frequency of Seroreactivity to Routinely Used Serologic Tests in Early-Treated Infants With HIV
Authors: Puthanakit Thanyawee , Ananworanich Jintanat , Akapirat Siriwat , Pattanachaiwit Supanit , Ubolyam Sasiwimol , Assawadarachai Vatcharain , Sawangsinth Panadda , Jupimai Thidarat , Anugulruengkitt Suvaporn , Tawan Monta , Kosalaraksa Pope , Borkird Thitiporn , Suntarattiwong Piyarat , Kanjanavanit Suparat , de Souza Mark S. ,   on behalf of the RV475/HIV-NAT209 Study Group
Published: January 2020

Background:

Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection.

Methods:

Fifty-eight HIV-infected infants treated with ART at a median age of 1.9 months (range: 0.2–5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies.

Results:

The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3–6 months (N = 15) showed a greater frequency (range: 53%–93%) and breadth (median and range: 3 [1–4]) of reactivity across the assays compared with those treated within 3 months (N = 43):16%–61% and breadth (1 [0–4]). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay.

Conclusions:

These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
HIV Status Disclosure and Sexual Transmission Risks Among People Who Are Living With HIV and Receiving Treatment for Non-HIV Sexually Transmitted Infections, Cape Town, South Africa
Authors: Kalichman Seth , Mathews Catherine , Banas Ellen , Kalichman Moira
Published: January 2020

Background:

HIV status disclosure to sex partners potentially reduces the risk of sexually transmitting HIV. However, there is limited information on the associations between HIV status disclosure in types of sexual partnerships and ensuing sexual practices.

Methods:

We examined HIV status disclosure to sex partners among 205 men and women living with HIV and receiving diagnostic and treatment services for a co-occurring sexually transmitted infection (STI) in Cape Town, South Africa. Participants completed partner-by-partner sexual behavior interviews and provided permission to extract recurrent STI clinic visits over the subsequent 12 months.

Results:

Three groups were formed on the basis of HIV status disclosure to sex partners: (1) 22% reported only HIV same-status partners, (2) 26% had HIV-negative or unknown HIV status (HIV different status) sex partners to whom they had disclosed their HIV status, and (3) 52% had at least one HIV different-status partner to whom they had not disclosed. There were no associations between HIV status disclosure and demographic characteristics, sexual practices, or recurrent STI clinic visits. Undisclosed HIV status to at least one HIV different-status sex partner was associated with greater alcohol use and less likelihood of receiving antiretroviral therapy; participants who were least likely to disclose their HIV status to partners drank more alcohol and were less likely to be taking antiretroviral therapy.

Conclusions:

High prevalence of partner nondisclosure and lack of significant correlates to HIV status disclosure indicate a need for further research with an eye toward identifying disclosure processes and mechanisms that may ultimately lead to effective interventions.
Brief Report: Persistence of Non-Vaccine Oncogenic HPV Genotypes in Quadrivalent HPV-Vaccinated Women Living With HIV
Authors: McClymont Elisabeth , Coutlée François , Lee Marette , Albert Arianne , Raboud Janet , Walmsley Sharon , Lipsky Nancy , Loutfy Mona , Trottier Sylvie , Smaill Fiona , Klein Marina B. , Yudin Mark H. , Harris Marianne , Wobeser Wendy , Bitnun Ari , Samson Lindy , Money Deborah ,   for the CTN 236 HPV in HIV Study Team
Published: January 2020

Background:

Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH.

Setting:

Multicentre, longitudinal cohort across Canada.

Methods:

WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose.

Results:

A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively).

Conclusions:

qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH.
Brief Report: Improving Early Infant Diagnosis Observations: Estimates of Timely HIV Testing and Mortality Among HIV-Exposed Infants
Authors: Webb Karen , Chitiyo Vivian , Mahachi Nyikadzino , Huruva Mukungunugwa Solomon , Mushavi Angela , Zizhou Simukai , Engelsmann Barbara , Abbas Ferrand Rashida , Neuman Melissa , Hartogensis Wendy , Geng Elvin
Published: January 2020

Background:

Improving efforts toward elimination of mother-to-child transmission of HIV requires timely early infant diagnosis (EID) among all HIV-exposed infants, but the occurrence of timely EID and infant survival may be underascertained in routine, facility-bound program data.

Methods:

From March 2015 to May 2015, we traced a random sample of HIV-positive mother and HIV-exposed infant pairs lost to follow-up for EID in facility registers in Zimbabwe. We incorporated updated information into weighted survival analyses to estimate incidence of EID and death. Reasons for no EID were surveyed from caregivers.

Results:

Among 2651 HIV-positive women attending antenatal care, 1823 (68.8%) infants had no documented EID by 3 months of age. Among a random sample of 643 (35.3%) HIV-exposed infants lost to follow-up for EID, vital status was ascertained among 371 (57.7%) and updated care status obtained from 256 (39.8%) mothers traced. Among all HIV-infected mother–HIV-exposed infant pairs, weighted estimates found cumulative incidence of infant death by 90 days of 3.9% (95% confidence interval: 3.4% to 4.4%). Cumulative incidence of timely EID with death as a competing risk was 60%. The most frequently cited reasons for failure to uptake EID were “my child died” and “I didn't know I should have my child tested.”

Conclusions:

Our findings indicate uptake of timely EID among HIV-exposed infants is underestimated in routine health information systems. High, early mortality among HIV-exposed infants underscores the need to more effectively identify HIV-positive mother–HIV exposed infant pairs at high risk of adverse outcomes and loss to follow-up for enhanced interventions.
Negative Diagnostic PCR Tests in School-Aged, HIV-Infected Children on Antiretroviral Therapy Since Early Life in Johannesburg, South Africa
Authors: Patel Faeezah , Thurman Cara , Liberty Afaaf , Burke Megan , Strehlau Renate , Shiau Stephanie , Coovadia Ashraf , Abrams Elaine J. , Violari Avy , Kuhn Louise
Published: January 2020

Background:

Younger age at antiretroviral therapy (ART) initiation has been associated with smaller HIV reservoirs. We investigated whether younger age of ART initiation is associated with testing negative and weaker signal on a standard HIV diagnostic test in treated children.

Methods:

At exit from a longitudinal study at 2 sites in Johannesburg, South Africa, 316 school-aged, HIV-infected children on continuous ART started at a median age of 6.3 months, were tested with standard total nucleic acid PCR used for infant diagnosis. All negative results were repeated. Simultaneous viral load (VL) and CD4+ T-cell counts/percentages, along with data collected over the prior 4 years, were used in multivariable regression to predict negative PCR results and higher cycle threshold (Ct) values (weaker signal).

Results:

Seven children (2.2%, 95% confidence interval: 0.6 to 3.8) in the full cohort had negative PCR results; all 7 were in a subset of 102 (6.9%, 95% confidence interval: 2.0 to 11.8) who had initiated ART at age 0–4 months and had VL <50 copies/mL at the time of PCR testing. Only one repeat tested as negative. Younger age at ART initiation, VL <50 copies/mL at time of test, sustained VL <400 copies/mL, lower CD4+ T-cell counts, and ever treated with efavirenz were significant predictors of weaker signal on the diagnostic test.

Conclusions:

In a small proportion of children who start ART in the first months of life and remain on continuous therapy, standard diagnostic HIV PCR tests may result as negative. Repeat testing may resolve uncertainty of diagnosis.
Immunological and Virological Responses in Older HIV-Infected Adults Receiving Antiretroviral Therapy: An Evidence-Based Meta-Analysis
Authors: Zhang Qi , Yu Xiaowen , Wu Tong , Shang Hong , Jiang Yongjun
Published: January 2020

Background:

Millions of people living with the HIV have received antiretroviral therapy (ART). Older adults make up a significant portion of these individuals; however, the immunological and virological responses to ART for older patients still need to be clarified.

Design:

Meta-analysis.

Methods:

In this article, we systematically reviewed research articles published between 2001 and 2018 that reported immunological and virological responses and AIDS-related mortality among HIV- infected adults (including individuals aged 50 years and older) receiving ART, using meta-analysis. ART efficiency was measured using 3 outcomes: (1) immunological response, (2) virological response, and (3) mortality.

Results:

We identified 4937 citations, and 40 studies were eventually selected to investigate ART efficiency in older HIV-infected patients, comprising more than 888,151 patients initiating ART. We report that older patients showed poor immunological responses, with CD4 counts and the restoration of CD4 counts after ART initiation being significantly lower than seen in younger patients. However, older patients exhibited better viral suppression rates (risk ratio: 1.04; 95% confidence intervals: 1.01 to 1.08) after 36 months following ART initiation. In addition, older adults had a higher risk of AIDS-related death (adjusted hazard ratio: 1.44, 95% confidence interval: 1.30 to 1.60).

Conclusions:

Older age after ART initiation was associated with a poorer immunological response and a higher risk of mortality, suggesting the need to increase early diagnosis and treatment among older HIV patients.
Characterizing Viral Load Burden Among HIV-Infected Women Around the Time of Delivery: Findings From Four Tertiary Obstetric Units in Gauteng, South Africa
Authors: Moyo Faith , Haeri Mazanderani Ahmad , Murray Tanya , Technau Karl-G. , Carmona Sergio , Kufa Tendesayi , Sherman Gayle G.
Published: January 2020

Background:

Elimination of mother-to-child transmission of HIV requires sustained viral load suppression during pregnancy and breastfeeding among women living with HIV (WLHIV). Antenatal antiretroviral therapy coverage is reported at >95% in South Africa, but viral load suppression rates are unknown. We describe maternal VL burden around time of delivery at 4 tertiary obstetric units (TOUs) in Gauteng Province.

Methods:

Between June 2018 and March 2019, routine point-of-care (PoC) maternal HIV VL and early infant diagnosis (EID) testing were implemented at 3 TOUs in Johannesburg and 1 in Tshwane district. WLHIV and HIV-exposed neonates were eligible for HIV VL (Xpert HIV-1 VL) and EID (Xpert HIV-1 EID or m-PIMA HIV1/2 detection) testing around time of delivery, respectively. Proportions of viremic women and intrauterine (IU)-infected neonates were calculated among valid PoC results.

Results:

Among 8147 live births to WLHIV, 2769 (34.0%) women and 4333 (53.2%) neonates had valid PoC results. Median VL at delivery was <40 copies/mL (interquartile range: 0–398). The proportion of women with a VL < 50, 50 to <1000, and ≥1000 copies/mL was 63.6%, 13.9% and 22.4%, respectively. There were 65/4333 (1.5%) IU-infected neonates. Among 1449 mother–neonate pairs with both VL and EID results, IU transmission by VL threshold was 3/946 (0.3%), 6/187 (3.2%), and 25/316 (7.9%) for VL < 50, 50 to <1000, and ≥1000 copies/mL, respectively (P < 0.001).

Conclusions:

Despite high antiretroviral therapy coverage, >1/3 of WLHIV had a VL ≥50 copies/mL at delivery. Among mother–neonate pairs, maternal VL ≥50 copies/mL accounted for 31/34 (91%) IU infections. Improvement in the quality of HIV care among WLHIV is essential if South Africa is to achieve elimination of mother-to-child transmission.
Raltegravir (RAL) in Neonates: Dosing, Pharmacokinetics (PK), and Safety in HIV-1–Exposed Neonates at Risk of Infection (IMPAACT P1110)
Authors: Clarke Diana F. , Acosta Edward P. , Cababasay Mae , Wang Jiajia , Chain Anne , Teppler Hedy , Popson Stephanie , Graham Bobbie , Smith Betsy , Hazra Rohan , Calabrese Kat , Bryson Yvonne , Spector Stephen A. , Lommerse Jos , Mirochnick Mark ,   the IMPAACT P1110 Protocol Team
Published: January 2020

Background:

Adequate pharmacokinetic and safety data in neonates are lacking for most antiretroviral agents. Raltegravir is a selective HIV-1 integrase strand transfer inhibitor available in a granule formulation suitable for use in neonates and young infants as prophylaxis or treatment of HIV infection.

Methods:

IMPAACT P1110 is a phase 1, multicenter, noncomparative dose-finding study of raltegravir in infants exposed to HIV-1 infection. A 2-cohort adaptive design was utilized where pharmacokinetic data from infants in cohort 1 who received 2 single doses of raltegravir 3 mg/kg were included in population modeling and simulations to guide selection of a daily dose for infants in cohort 2.

Results:

A total of 52 infants enrolled in IMPAACT 1110: cohort 1 (N = 16) and cohort 2 (N = 36). Using simulations based on population PK modeling incorporating cohort 1 data, the following daily dosing regimen was selected for study: 1.5 mg/kg daily from birth through day 7; 3 mg/kg twice daily from days 8–28 of life; and 6 mg/kg twice daily after 4 weeks of age through 6 weeks of age. The geometric mean protocol exposure targets for AUC, Ctrough, and Cmax were met or slightly exceeded in all infants. The chosen neonatal raltegravir dosing regimen was safe and well tolerated in full-term neonates during treatment over the first 6 weeks of life and follow-up to age 24 weeks.

Conclusions:

Raltegravir can be safely administered to full-term infants using the daily dosing regimen studied. This regimen is not recommended for use in premature infants in a new version of P1110.
Skeletofacial Reconstruction for Cleft-Related Deformities
Authors: Denadai Rafael , Chou Pang-Yun , Pai Betty C. J. , Chen Chit , Cheng-Hui Lin Clement , Huang Chiung-Shing , Chen Yu-Ray , Lo Lun-Jou
Published: January 2020

Skeletofacial reconstruction in skeletally mature patients with cleft lip/palate can be challenging because of multifaceted condition-specific anatomical features in addition to several repercussions from surgical intervention during the growing period. This surgical report presents the history and evolving philosophy of cleft-skeletofacial reconstruction at the Chang Gung Craniofacial Center, a referral center for cleft care in Taiwan. The maximization of satisfactory function and the appearance outcome-burden ratio have been the fundamental aims for this team to develop and upgrade cleft-skeletofacial reconstruction over the past 4 decades, with more than 10,000 mature patients treated. The study highlights key lessons learned in outcome-based and patient-oriented changes over time until the current approach, which focuses on patient-centered care with a comprehensive, multidisciplinary, and team-based model. Substantial advances in surgical, orthodontic, anesthetic, and computer imaging aspects have contributed to improving and optimizing the correction of a broad spectrum of facial and occlusal deformities while ensuring safety, predictability, efficiency, and stability in outcomes. Understanding the development and refinement of cleft-skeletofacial reconstruction over the time and transferring these time-tested and scientifically validated protocols and principles to clinical practice may serve as a reliable foundation to continue the advancement and enhancement of the delivery of surgical cleft care worldwide.
True and Average Internal Nasal Valve Area in Septorhinoplasty
Authors: Zeina Ahmed M. , El Zeheiry Ahmed M. , Bahaa El-Din Ahmed M.
Published: January 2020

The internal nasal valve provides most of the upper airway resistance; therefore, many surgical techniques have been developed to reconstruct and widen this sensitive area of the nasal airway. Twenty patients participated in this study to compare the effects of 2 techniques (spreader grafts and modified spreader flap) on the true valve area and the average valve area after rhinoplasty according to standard axial computed tomography on admission and 6 months following the surgery. The mean follow-up time was 10.2 months. After rhinoplasty, the average valve area increased in all patients who underwent the spreader graft or modified spreader flap techniques. The preoperative average valve areas for patients undergoing the spreader graft and spreader flap techniques were (37.10 ± 16.45 mm2) and (36.86 ± 10.56 mm2), respectively, whereas the postoperative results were (48.58 ± 12.85 mm2) for those who underwent the spreader graft technique and (56.22 ± 19.06 mm2) for those who underwent the modified spreader flap technique. Both techniques resulted in significant radiological and clinical improvement with a good correlation between the subjective and objective tests.

Level of Evidence

IV.
Capgras Syndrome in the Young
Authors: Ng Kok Pin , Wong Benjamin , Xie Wanying , Kandiah Nagaendran
Published: January 2020

This is a case report of an atypical presentation of early onset Alzheimer disease (EOAD) in a young patient with Capgras syndrome and cognitive impairment. The concurrent onset of psychiatric and cognitive symptoms prompted a detailed evaluation for a neurodegenerative disease. A 50-year-old male lawyer presented with low mood, apathy, delusions, and auditory hallucinations over 18 months. He considered his wife as an imposter and would require her text message to confirm her identity. He became more forgetful and had to give up his law practice. His neuropsychological assessment was impaired in all domains. Genetic testing revealed homozygosity for APOEe4 alleles. His magnetic resonance imaging showed predominant parietal and medial temporal atrophy, [18F]Fluorodeoxyglucose positron emission tomography showed frontal, parietal and posterior temporal hypometabolism and [18F]Flutemetamol positron emission tomography was positive for amyloid deposition, leading to the diagnosis of EOAD. This case highlights EOAD as a differential diagnosis in young patients who present with Capgras syndrome.
Vladimir Sertić: forgotten pioneer of virology and bacteriophage therapy
Authors: Lacković Zdravko , Toljan Karlo
Published: January 2020

Vladimir Sertić was a pioneer of bacteriophage research in the period between the two world wars. He was born and educated in Croatia, where he made his initial discoveries, and joined Félix d'Herelle's Laboratoire du Bactériophage in Paris in 1928. Original documents and a box with hundreds of sealed bacteriophage
s
samples were kept in Sertić's Zagreb home for decades. Following Vladimir's death, his sister passed this archival material to Professor Zdravko Lacković in 1989. Some years later, these artefacts were opened and studied. Additionally, we conducted a literature search using the term ‘Vladimir Sertić’ in the databases PubMed and Google Scholar. After a detailed examination of these data, we established a chronology of his work and compiled a list of his scientific publications. A complete bibliography, with the exception of those publications already cited here, is provided as an appendix. Sertić's key contributions included the exploration of the properties of phage lysins, the devising of a uniform bacteriophage classification system and, in collaboration with his protégé, Nikolai Boulgakov, the isolation of numerous bacteriophage strains, including the famous φX174. Finally it was Sertić's pioneering work in Zagreb that offered confirmation that phages are live agents.
The variation of grain size distribution in rock granular material in seepage process considering the mechanical–hydrological–chemical coupling effect: an experimental research
Authors: Kong Hailing , Wang Luzhen , Zhang Hualei
Published: January 2020

As a common solid waste in geotechnical engineering, rock granular material should be properly treated and recycled. Rock granular material often coexists with water when it is used as the filling material in geotechnical engineering. Water flowing in rock granular materials is a complex progress with the mechanical–hydrological–chemical (MHC) coupling effect, i.e. the water scours in the gaps and spaces in the rock granular material structure, produces chemical reactions with rock grains, rock grains squeeze each other under the water pressure and compression leading to re-breakage and producing secondary rock grains, and the fine rock grains are migrated with water and rushed out. In this process, rock grain size distribution (GSD) changes, it affects the physical and mechanical characteristics of the rock granular materials, and even influences the seepage stability of the rock granular materials. To study the variation of GSD in the rock granular material considering the MHC coupling effect after the seepage process, seepage experiments of rock grain samples are carried out and analysed in this paper. The result is expected to have a positive impact on further studies of the properties of the rock granular material.
Compressor performance modelling method based on support vector machine nonlinear regression algorithm
Authors: Ying Yulong , Xu Siyu , Li Jingchao , Zhang Bin
Published: January 2020

To overcome the difficulty of having only part of compressor characteristic maps including on-design operating point, and accurately calculate compressor thermodynamic performance under variable working conditions, this paper proposes a novel compressor performance modelling method based on support vector machine nonlinear regression algorithm. It is compared with the other three neural network algorithms (i.e. back propagation (BP), radial basis function (RBF) and Elman neural networks) from the perspective of interpolation and extrapolation accuracy as well as calculation time, to prove the validity of the proposed method. Application analyses indicate that the proposed method has better interpolation and extrapolation performance than the other three neural networks. In terms of flow characteristic map representation, the root mean square error (RMSE) of the extrapolation performance at higher and lower speed operating area by the proposed method is 0.89% and 2.57%, respectively. And the total RMSE by the proposed method is 2.72%, which is more accurate by 47% than the Elman algorithm. For efficiency characteristic map representation, the RMSE of the extrapolation performance at higher and lower speed operating area by the proposed method is 2.85% and 1.22%, respectively. And the total RMSE by the proposed method is 1.81%, which is more accurate by 35% than the BP algorithm. Moreover, the proposed method has better real-time performance compared with the other three neural network algorithms.
Host density drives viral, but not trypanosome, transmission in a key pollinator
Authors: Bailes Emily J. , Bagi Judit , Coltman Jake , Fountain Michelle T. , Wilfert Lena , Brown Mark J. F.
Published: January 2020

Supplemental feeding of wildlife populations can locally increase the density of individuals, which may in turn impact disease dynamics. Flower strips are a widely used intervention in intensive agricultural systems to nutritionally support pollinators such as bees. Using a controlled experimental semi-field design, we asked how density impacts transmission of a virus and a trypanosome parasite in bumblebees. We manipulated bumblebee density by using different numbers of colonies within the same area of floral resource. In high-density compartments, slow bee paralysis virus was transmitted more quickly, resulting in higher prevalence and level of infection in bumblebee hosts. By contrast, there was no impact of density on the transmission of the trypanosomeCrithidia bombi, which may reflect the ease with which this parasite is transmitted. These results suggest that agri-environment schemes such as flower strips, which are known to enhance the nutrition and survival of bumblebees, may also have negative impacts on pollinators through enhanced disease transmission. Future studies should assess how changing the design of these schemes could minimize disease transmission and thus maximise their health benefits to wild pollinators.
Lens transmittance shapes ultraviolet sensitivity in the eyes of frogs from diverse ecological and phylogenetic backgrounds
Authors: Yovanovich Carola A. M. , Pierotti Michele E. R. , Kelber Almut , Jorgewich-Cohen Gabriel , Ibáñez Roberto , Grant Taran
Published: January 2020

The amount of short wavelength (ultraviolet (UV), violet and blue) light that reaches the retina depends on the transmittance properties of the ocular media, especially the lens, and varies greatly across species in all vertebrate groups studied previously. We measured the lens transmittance in 32 anuran amphibians with different habits, geographical distributions and phylogenetic positions and used them together with eye size and pupil shape to evaluate the relationship with diel activity pattern, elevation and latitude. We found an unusually high lens UV transmittance in the most basal species, and a cut-off range that extends into the visible spectrum for the rest of the sample, with lenses even absorbing violet light in some diurnal species. However, other diurnal frogs had lenses that transmit UV light like the nocturnal species. This unclear pattern in the segregation of ocular media transmittance and diel activity is shared with other vertebrates and is consistent with the absence of significant correlations in our statistical analyses. Although we did not detect a significant phylogenetic effect, closely related species tend to have similar transmittances, irrespective of whether they share the same diel pattern or not, suggesting that anuran ocular media transmittance properties might be related to phylogeny.
Salinigranum halophilum sp. nov., isolated from marine solar salterns
Authors: Zhao Yang-Jie , Tao Cong-Qi , Zeng Chun-Lin , Zhu Lin , Cui Heng-Lin
Published: January 2020

Three halophilic archaeal strains, YJ-53T, ZS-5 and DYF38, were isolated from marine solar salterns located in different provinces of China. The three strains formed a single cluster (99.7–99.8 and 97.9–99.2 % similarities, respectively) that was separate from the current two members of

Salinigranum

(96.7–98.0 and 89.8–92.9 % similarities, respectively) on the basis of 16S rRNA and rpoB′ gene sequence comparisons and phylogenetic analysis. Diverse phenotypic characteristics differentiated strains YJ-53T, ZS-5 and DYF38 from

Salinigranum rubrum

GX10T and

Salinigranum salinum

YJ-50-S2T. The major polar lipids of isolated strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and two major glycolipids chromatographically identical to mannosyl glucosyl diether and sulfated mannosyl glucosyl diether, detected in the current members of

Salinigranum

. The OrthoANI and in silico DNA–DNA hybridization (DDH) values between the three strains were in the range of 97.7–98.4 % and 80.3–86.1 %, respectively, much higher than the threshold values proposed as species boundaries (average nucleotide identity 95–96 % and in silico DDH 70 %), revealing that the three strains represent one species. Results of comparative OrthoANI and in silico DDH analyses of the strains described in this study with validly described members of the genus

Salinigranum

supported that strains YJ-53T (=CGMCC 1.12860T=JCM 30238T), ZS-5 (=CGMCC 1.12867=JCM 30240) and DYF38 (=CGMCC 1.13779=JCM 33557) represent a novel species of the genus

Salinigranum

, for which the name Salinigranum halophilum sp. nov. is proposed.
Paracoccus aeridis sp. nov., an indole-producing bacterium isolated from the rhizosphere of an orchid, Aerides maculosa
Authors: Rai Anusha , N Smita , G Suresh , A Shabbir , G Deepshikha , Ch Sasikala , Ch.V Ramana
Published: January 2020

A Gram-stain-negative, non-motile, coccoid-shaped, catalase- and oxidase-positive, non-denitrifying, neutrophilic bacterium designated as strain JC501T was isolated from an epiphytic rhizosphere of an orchid, Aerides maculosa, growing in the Western Ghats of India. Phylogenetic analyses based on the 16S rRNA gene sequence indicated that strain JC501T belonged to the genus

Paracoccus

and had the highest levels of sequence identity with

Paracoccus marinus

KKL-A5T (98.9 %),

Paracoccus contaminans

WPAn02T (97.3 %) and other members of the genus

Paracoccus

(<97.3 %). Strain JC501T produced indole-3 acetic acid and other indole derivatives from tryptophan. The dominant respiratory quinone was Q-10 and the major fatty acid was C18 : 1ω7c/C18 : 1ω6c, with significant quantities of C18 : 1ω9c, C17 : 0 and C16 : 0. The polar lipids of strain JC501T comprised phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, an unidentified glycolipid, two unidentified aminolipids, two unidentified lipids and four unidentified phospholipids. The genome of strain JC501T was 3.3 Mbp with G+C content of 69.4 mol%. For the resolution of the phylogenetic congruence of the novel strain, the phylogeny was also reconstructed with the sequences of eight housekeeping genes. Based on the results of phylogenetic analyses, low (<85.9 %) average nucleotide identity, digital DNA–DNA hybridization (<29.8 %), chemotaxonomic analysis and physiological properties, strain JC501T could not be classified into any of the recognized species of the genus

Paracoccus

. Strain JC501T represents a novel species, for which the name Paracoccus aeridis sp. nov. is proposed. The type strain is JC501T (=LMG 30532T=NBRC 113644T).
Redox response of iron-sulfur glutaredoxin GRXS17 activates its holdase activity to protect plants from heat stress
Authors: Martins Laura , Knuesting Johannes , Bariat Laetitia , Dard Avilien , Freibert Sven A. , Marchand Christophe H. , Young David , Dung Nguyen Ho Thuy , Debures Anne , Saez-Vasquez Julio , Lemaire Stéphane D. , Lill Roland , Messens Joris , Scheibe Renate , Reichheld Jean-Philippe , Riondet Christophe
Published: January 2020

Living organisms use a large panel of mechanisms to protect themselves from environmental stress. Particularly, heat stress induces misfolding and aggregation of proteins which are guarded by chaperone systems. Here, we examine the function the glutaredoxin GRXS17, a member of thiol reductases families in the model plantArabidopsis thaliana. GRXS17 is a nucleocytosolic monothiol glutaredoxin consisting of an N-terminal thioredoxin (TRX)-domain and three CGFS-active site motif-containing GRX-domains that coordinate three iron-sulfur (Fe-S) clusters in a glutathione (GSH)-dependent manner. As a Fe-S cluster-charged holoenzyme, GRXS17 is likely involved in the maturation of cytosolic and nuclear Fe-S proteins. In addition to its role in cluster biogenesis, we showed that GRXS17 presents both foldase and redox-dependent holdase activities. Oxidative stress in combination with heat stress induces loss of its Fe-S clusters followed by subsequent formation of disulfide bonds between conserved active site cysteines in the corresponding TRX domains. This oxidation leads to a shift of GRXS17 to a high-MW complex and thus, activates its holdase activity. Moreover, we demonstrate that GRXS17 is specifically involved in plant tolerance to moderate high temperature and protects root meristematic cells from heat-induced cell death. Finally, we showed that upon heat stress, GRXS17 changes its client proteins, possibly to protect them from heat injuries. Therefore, we propose that the iron-sulfur cluster enzyme glutaredoxin GRXS17 is an essential guard to protect proteins against moderate heat stress, likely through a redox-dependent chaperone activity. All in all, we reveal the mechanism of an Fe-S cluster-dependent activity shift, turning the holoenzyme GRXS17 into a holdase that prevents damage caused by heat stress.
MAnorm2 for quantitatively comparing groups of ChIP-seq samples
Authors: Tu Shiqi , Li Mushan , Tan Fengxiang , Chen Haojie , Xu Jian , Waxman David J. , Zhang Yijing , Shao Zhen
Published: January 2020

Eukaryotic gene transcription is regulated by a large cohort of chromatin associated proteins, and inferring their differential binding sites between cellular contexts requires a rigorous comparison of the corresponding ChIP-seq data. We present MAnorm2, a new computational tool for quantitatively comparing groups of ChIP-seq samples. MAnorm2 uses a hierarchical strategy to normalize ChIP-seq data and then performs differential analysis by assessing within-group variability of ChIP-seq signals under an empirical Bayes framework. In this framework, MAnorm2 considers the abundance of differential ChIP-seq signals between groups of samples and the possibility of different within-group variability between groups. When samples in each group are biological replicates, MAnorm2 can reliably identify differential binding events even between highly similar cellular contexts. Using a number of real ChIP-seq data sets, we observed that MAnorm2 clearly outperformed existing tools for differential ChIP-seq analysis, with the improvement in performance being most dramatic when the groups of samples being compared had distinct global within-group variability.
Targeting a critical step in fungal hexosamine biosynthesis
Authors: Lockhart Deborah E.A. , Stanley Mathew , Raimi Olawale G. , Robinson David A. , Boldovjakova Dominika , Squair Daniel R. , Ferenbach Andrew T. , Fang Wenxia , van Aalten Daan M.F.
Published: January 2020

Aspergillus fumigatusis a human opportunistic fungal pathogen with a cell wall that protects it from the extracellular environment. Chitin, an essential cell wall component, is synthesised from UDP-GlcNAc that is produced by the hexosamine biosynthetic pathway. Here, we provide genetic and chemical evidence that glucosamine 6-phosphateN-acetyltransferase (Gna1), a key enzyme in this pathway, is an exploitable antifungal drug target. Deletion ofGNA1results in loss of viability and disruption of the cell wall, phenotypes that can be rescued by the product of the enzyme. In a murine model of aspergillosis, theΔgna1mutant strain attenuates virulence. Using a fragment-based approach, we discovered a small heterocyclic scaffold that binds proximal to the active site and can be optimised to a selective sub-micromolar binder. Taken together, we have provided genetic, structural and chemical evidence for Gna1 as an antifungal target inAspergillus fumigatus.
Human cytomegalovirus evades ZAP detection by suppressing CpG dinucleotides in the major immediate early genes
Authors: Lin Yao-Tang , Chiweshe Stephen , McCormick Dominique , Raper Anna , Wickenhagen Arthur , DeFillipis Victor , Gaunt Eleanor , Simmonds Peter , Wilson Sam J , Grey Finn
Published: January 2020

The genomes of RNA and small DNA viruses of vertebrates display significant suppression of CpG dinucleotide frequencies. Artificially increasing dinucleotide frequencies results in substantial attenuation of virus replication, suggesting that these compositional changes may facilitate recognition of non-self RNA sequences. Recently, the interferon inducible protein ZAP, was identified as the host factor responsible for sensing CpG in viral RNA, through direct binding and possibly downstream targeting for degradation. Using an arrayed interferon stimulated gene expression library screen, we identified ZAPS, and its associated factor TRIM25, as direct inhibitors of human cytomegalovirus (HCMV) replication. Exogenous expression of ZAPS and TRIM25 significantly reduced virus replication while knockdown resulted in increased virus replication. HCMV displays a strikingly heterogeneous pattern of CpG representation with a specific suppression of CpGs within the IE1 major immediate early transcript which is absent in subsequently expressed genes. We demonstrated that suppression of CpG dinucleotides in the IE1 gene allows evasion of inhibitory effects of ZAP. During HCMV infection, expression of ZAP and TRIM25 are rapidly reduced, removing pressure to suppress dinucleotide frequencies in viral genes expressed after the immediate early genes, while acute virus replication and high levels of ZAP are mutually exclusive. Finally, we show that TRIM25 regulates alternative splicing between the ZAP short and long isoforms during HCMV infection and interferon induction, with knockdown of TRIM25 resulting in decreased ZAPS and corresponding increased ZAPL expression. These results demonstrate for the first time that ZAP is a potent host restriction factor against large DNA viruses and that HCMV evades ZAP detection through suppression of CpG dinucleotides within the major immediate early transcripts. Furthermore, TRIM25 is required for efficient upregulation of the interferon inducible short isoform of ZAP through regulation of alternative splicing.