bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Recombinant Strains of Potato Virus Y in Seed Potato Planted in Idaho and Washington States Between 2011 and 2021
Authors: Tran Lisa T. , Green Kelsie J. , Rodriguez-Rodriguez Mariana , Orellana Gardenia E. , Funke Cassandra N. , Nikolaeva Olga V. , Quintero-Ferrer Arturo , Chikh-Ali Mohamad , Woodell Lynn , Olsen Nora , Karasev Alexander V.
Published: October 2021

Potato virus Y (PVY) has emerged as the main reason for potato seed lot rejections, seriously affecting seed potato production in the United States throughout the past 20 years. The dynamics of PVY strain abundance and composition in various potato growing areas of the United States has not been well documented or understood up to now. The objective of this study was to find out the prevalence of PVY strains in potato fields in the Pacific Northwest (PNW), including seed potato production systems in the State of Idaho and commercial potato fields in the Columbia Basin of Washington State between 2011 and 2021. Based on the testing of >10,000 foliar samples during Idaho seed certification winter grow-out evaluations of seed potato lots and seed lot trials in Washington State, a dramatic shift in the PVY strain composition was revealed in the PNW between 2011 and 2016. During this time period, the prevalence of the ordinary, PVYO strain in seed potato dropped 8- to 10-fold, concomitantly with the rise of recombinant strains PVYN-Wi and PVYNTNa, which together accounted for 98% of all PVY positives by 2021. In Idaho seed potato, PVYNTNa strain associated with the potato tuber necrotic ringspot disease (PTNRD) was found to increase threefold between 2011 and 2019, accounting for 24% of all PVY positives in 2019. Mild foliar symptoms induced by recombinant PVY strains may be partially responsible for the proliferation of PVYN-Wi and PVYNTNa in potato crops. A spike of another PTNRD-associated recombinant, PVY-NE11, was recorded in the PNW between 2012 and 2016, but after reaching a 7 to 10% level in 2012 to 2013 this recombinant disappeared from the PNW potato by 2019. Whole genome sequence analysis of the PVY-NE11 suggested this recombinant was introduced in the United States at least three times. The data on PVY strain abundance in the PNW potato crops suggest that virus management strategies must consider the current dominance of the two recombinant PVY strains, PVYN-Wi and PVYNTNa.
Analysis of Grapevine’s Somatic Embryogenesis Receptor Kinase (SERK) Gene Family: VqSERK3/BAK1 Overexpression Enhances Disease Resistance
Authors: Li Yajuan , Jiao Chen , Wei Zhenjiang , Chai Shengyue , Jia Hui , Gao Min , Allison Jessica , Li Zhi , Song Chang-bing , Wang Xiping
Published: October 2021

The somatic embryogenesis receptor kinase (SERK) gene family has been intensively studied in several plant species. Here we confirmed the existence of five SERK genes in grapevine (Chinese wild grapevine Vitis quinquangularis) and named them VqSERK1, VqSERK2, VqSERK3, VqSERK4, and VqSERK5. Analysis of the predicted structures of these SERK proteins revealed they include a signal peptide domain, a leucine zipper domain, a Ser-Pro-Pro domain, a single transmembrane domain, different leucine-rich repeats, and an intracellular kinase activity domain. The SERK genes of grapevine showed different gene expression patterns when treated with powdery mildew (Erysiphe necator) and hormones (salicylic acid, jasmonic acid, abscisic acid, and ethylene). Subcellular localization assays confirmed that VqSERK family proteins localized to the cell membrane. Moreover, we cloned the SERK3/BAK1 gene from the Chinese wild grapevine V. quinquangularis clone ‘Shang-24’. Heterologous VqSERK3/BAK1 expression in the Arabidopsis bak1-4 mutant lines restored control of cell death, increased resistance to powdery mildew, and strengthened stomatal immunity. Our work may provide the foundation for further studies of SERK genes for pathogen resistance and hormone treatment in grapevine.
The Impact of Diaphorina citri-Vectored ‘Candidatus Liberibacter asiaticus’ on Citrus Metabolism
Authors: Padhi Emily M. T. , Araujo Karla J. , Mitrovic Elizabeth , Polek Marylou , Godfrey Kris E. , Slupsky Carolyn M.
Published: October 2021

‘Candidatus Liberibacter asiaticus’ is associated with the devastating citrus disease Huanglongbing (HLB). It is transmitted by grafting infected material to healthy plants and by the feeding of the Asian citrus psyllid (Diaphorina citri). Previously, we demonstrated that a metabolomics approach using proton-nuclear magnetic resonance spectroscopy discriminates healthy from diseased plants via grafting. This work assessed the capability of this technology in discriminating healthy and diseased plants when the bacterium is vectored by psyllids. One-year-old greenhouse-grown ‘Lisbon’ lemon trees were exposed to either carrier psyllids (exposed, n = 10), or psyllids that were free of ‘Candidatus Liberibacter asiaticus’ (control, n = 6). Leaf metabolites were tracked for 1 year and disease diagnosis was made using quantitative PCR. Overall, 31 water-soluble metabolites were quantified in leaves, including four sugars and 12 amino acids. Analysis via nonmetric multidimensional scaling and principal component analysis revealed significant differences between the leaf metabolome of control versus infected trees beginning at 8 weeks postexposure, including alterations in glucose and quinic acid concentrations. These findings provide a longitudinal overview of the metabolic effects of HLB during the early phases of disease, and confirm previous experimental work demonstrating that infection elicits changes in the leaf metabolome that enables discrimination between healthy and infected plants. Here we demonstrate that the mode of inoculation (i.e., graft versus psyllid) results in a similar pathology.
Molecular and Chemical Screening for Inherent Disease Resistance Factors of Norway Spruce (Picea abies) Clones Against Conifer Stem Rot Pathogen Heterobasidion parviporum
Authors: Liu Mengxia , Wang Kai , Ghimire Rajendra P. , Haapanen Matti , Kivimäenpää Minna , Asiegbu Fred O.
Published: October 2021

Root and stem rot of conifer trees caused by Heterobasidion annosum species complex leads to huge economic losses in Europe, yet not much is known about the molecular and chemical basis for host resistance. To identify inherent chemical or molecular markers in clones found to be either resistant or susceptible, we sampled needle tissues of all the clones before pathogen inoculation. We conducted a short-term resistance screening by using the pathogen H. parviporum to inoculate 70 Norway spruce clones. Based on lesion size, subsets of highly susceptible and resistant clones were further analyzed. Terpene detection and RNA sequencing were performed to explore inherent variations in genotypes differing in resistance to pathogenic challenge at chemical and transcriptional levels. A negative correlation emerged between resistance and growth. Terpene profiles of resistant clones showed higher content of monoterpenes and sesquiterpenes, with concomitant increased transcript abundance of genes involved in the terpenoid pathway. A set of upregulated genes relevant to flavonoid biosynthesis was observed in resistant genotypes, whereas higher transcripts of lignin biosynthetic genes were prevalent in susceptible clones. Genes involved in flavonoid and lignin biosynthesis as well as terpene content may have a role in facilitating resistance of Norway spruce against H. parviporum. Our results provide strong support on the feasibility of sampling needle tissues before pathogen inoculation, and the approach could be of value for large-scale screening of novel biomarkers for durable resistance. The additional insights could form a basis for further research on resistance screening in this pathosystem.
Treatment of small cell lung cancer: recent advances
Authors: Chu Xiangling , Han Chaonan , Su Chunxia
Published: October 2021

Purpose of review

In this article, we aimed to summarize the recent progress being made in treatment of small cell lung cancer (SCLC).

Recent findings

SCLC is characterized by strong invasiveness, easy recurrence and early metastasis. In recent years, the emergence of immune checkpoint inhibitors (ICIs) therapy has broken the deadlock in the treatment field of SCLC. Combination strategies, such as the addition of ICIs to chemotherapy and radiotherapy, are actively underway. Some of these strategies have yielded significant survival benefits and tolerable adverse events, whereas several of them have failed with no significant improvement. In addition, the new classification of SCLC based on genomic analysis has deepened the understanding of SCLC and suggested new therapeutic directions. Similarly, the discovery of some new therapeutic targets, such as DDL3, CDK7 and PARP, also brings new hope for improving the survival of patients with SCLC.

In this article, we will review the recent advances of therapeutic regimen for patients with SCLC. Following the revolutionary success of adding ICIs to chemotherapy, more varieties of combination strategies have been explored in recent trials. In addition, therapeutic drug research and efficacy evaluation against for new targets are under investigation. Altogether, progress on genomic analysis, investigation of biological pathways and treatment regimen combination are providing renewed hope for patients with SCLC.
Regularity and Timing of Sleep Patterns and Behavioral Health Among Adolescents
Authors: Lunsford-Avery Jessica R. , Wang Ke (Will) , Kollins Scott H. , Chung Richard J. , Keller Casey , Engelhard Matthew M.
Published: October 2021

Objective:

Sleep is vital to supporting adolescent behavioral health and functioning; however, sleep disturbances remain under-recognized and undertreated in many health care settings. One barrier is the complexity of sleep, which makes it difficult for providers to determine which aspects—beyond sleep duration—may be most important to assess and treat to support adolescent health. This study examined associations between 2 sleep indices (regularity and timing) and adolescent behavioral health and functioning over and above the impact of shortened/fragmented sleep.

Method:

Eighty-nine adolescents recruited from the community (mean age = 14.04, 45% female participants) completed 7 days/nights of actigraphy and, along with a parent/guardian, reported on behavioral health (internalizing and externalizing symptoms) and psychosocial functioning. Stepwise linear regressions examined associations between sleep timing and regularity and behavioral/functional outcomes after accounting for shortened/fragmented sleep.

Results:

Delayed sleep timing was associated with greater self-reported internalizing (F[6,82] = 11.57, p = 0.001) and externalizing (F[6,82] = 11.12, p = 0.001) symptoms after accounting for shortened/fragmented sleep. Irregular sleep was associated with greater self-reported and parent-reported externalizing symptoms (self: F[7,81] = 6.55, p = 0.01; parent: F[7,80] = 6.20, p = 0.01) and lower psychosocial functioning (self: F[7,81] = 6.03, p = 0.02; parent: F[7,78] = 3.99, p < 0.05) after accounting for both shortened/fragmented sleep and delayed sleep timing.

Conclusion:

Sleep regularity and timing may be critical for understanding the risk of poor behavioral health and functional deficits among adolescents and as prevention and intervention targets. Future work should focus on developing and evaluating convenient, low-cost, and effective methods for addressing delayed and/or irregular adolescent sleep patterns in real-world health care settings.
Infant Mental Health Home Visiting Mitigates Impact of Maternal Adverse Childhood Experiences on Toddler Language Competence: A Randomized Controlled Trial
Authors: Riggs Jessica L. , Rosenblum Katherine L. , Muzik Maria , Jester Jennifer , Freeman Sarah , Huth-Bocks Alissa , Waddell Rachel , Alfafara Emily , Miller Alison , Lawler Jamie , Erickson Nora , Weatherston Debbie , Shah Prachi , Brophy-Herb Holly ,   the Michigan Collaborative for Infant Mental Health Research
Published: October 2021

Objective:

The goal of this study was to test the impact of maternal adverse childhood experiences (ACEs) on subsequent child language competence; higher parental ACEs were expected to predict risk of toddler language delay. Participation in Infant Mental Health Home Visiting (IMH-HV) treatment, which aims to enhance responsive caregiving and improve child social-emotional development, was expected to mitigate this association.

Methods:

A randomized controlled trial (RCT) design was used. ACEs data were collected at baseline. Child language screening (using the Preschool Language Scales Screening Test) was conducted 12 months later by masters-level evaluators who were blind to treatment condition. Visits occurred in participants' homes. Participants were community-recruited and were randomized to treatment (psychotherapeutic IMH-HV) or control (treatment as usual). Data come from 62 families who participated in all waves of an RCT testing the efficacy of IMH-HV; mothers were eligible based on child age (<24 mo at enrollment) and endorsement of ≥2 sociodemographic eligibility criteria (economic disadvantage, depression, perceived parenting challenges, and/or high ACEs).

Results:

The age of mothers enrolled in this ranged from 19 to 44 years (M = 31.91; SD = 5.68); child age at baseline ranged from prenatal to 26 months (M = 12.06; SD = 6.62). The maternal ACE score predicted child language competence (t (5,55) = −3.27, p = 0.002). This effect was moderated by treatment (t (6,54) = 1.73, p = 0.04), indicating no association between maternal ACEs and child language for those randomized to IMH-HV.

Conclusion:

The results highlight that the effects of parent ACEs on early childhood outcomes may be buffered by participation in psychotherapeutic home visiting (trial registration: NCT03175796).
Youth, Caregiver, and Provider Perception of the Transition from Pediatric to Adult Care for Youth with Chronic Diseases
Authors: Tsang Vivian W. L. , Fletcher Sarah , Jassemi Sara , Smith Sharon
Published: October 2021

Objective:

Youth with chronic diseases are required to transition from pediatric to adult care across the world at variable ages in their adolescent years. The aim of this study is to examine perspectives of young patients, caregivers, and physicians in the transition process.

Methods:

This 3-phase mixed methods research study gathered data using an iterative approach with the collaboration of youth coresearchers. Physician opinions were gathered through a survey. Further data were collected through 15 semistructured, standardized interviews of adolescent medicine physicians. Perspectives of adolescents and young adult (AYA) patients and their caregivers were gathered independently using a 20-item survey. Quantitative data were analyzed with descriptive statistics and sorted by theme.

Results:

In phase 1, respondents rated current transition processes as an average 5.19/10 on a 10-point Likert scale (1 = poor and 10 = excellent) with no participants rating 9 or 10 of 10. The top barrier identified was a lack of communication between pediatric and adult doctors (71.0%). The top ranked strategy for improvement was to provide formal transition guidelines (69.8%). In phase 2, specific concerns include lack of insurance coverage, lack of physicians available to take on youth transitioning to adult care who are also knowledgeable regarding pediatric conditions, and lack of funding or staff support for transition clinics. In phase 3, most of the youth surveyed (52%) reported that their physicians have not involved them in conversations about transitioning. AYA patients prefer the point of transfer to occur with other life transitions such as graduation, and caregivers prefer transfer to happen during times of stability where their children can dedicate adequate time to their health.

Conclusion:

Fulfilling youth desire for increased patient autonomy and ownership can help overcome their poor perception of the transition process. Increased physician training in adolescent health and improvements in post-transition community plans may be beneficial to prevent loss to follow-up among young patients across medical disciplines. Successful transition into adult care requires a unique process for each youth and requires adequate preparation from the pediatric front, empowerment of young patients and their families, and continuity of care by adult providers.
Challenge of surviving COPD with COVID-19 patient: review of the literature with unusual case report
Authors: Essa Rawand A. , Ahmed Sirwan K. , Bapir Dunya H. , Rasul Shero A. , Khdir Awat A. , Abubakr Chawan P.
Published: October 2021

Chronic obstructive pulmonary disease (COPD) refers to limitation of air flow and presence of persistent respiratory symptoms due to abnormalities in the airway or alveolar airway. COVID-19 patients with COPD have a higher mortality and morbidity. Recent studies revealed that present smokers have a higher risk mortality rate than the former and never smokers. However, COPD patients infected with SARS-CoV-2 have a low survival rate during the COVID-19 pandemic. Here we present a case of COVID-19 in a patient with COPD. The patient presented with shortness of breath, altered mental status, and loss of consciousness and 3 days prior was diagnosed with COVID-19, by reverse transcription polymerase chain reaction. The patient diagnosed by physical, and laboratory findings, and treated by giving 2 L/min oxygen on a ventilator pressure control ventilation mode, with administered antibiotic, antipyretic, proton pump inhibitors, and mucolytic drugs without complications. COVID-19 incidence is increased when there are other illnesses present, such as COPD. Based on 18 studies of 26,075 cases reporting, COPD was significantly associated with an increased risk of adverse outcomes in COVID-19 patients, particularly current smokers. We report a case of COVID-19, heavy smoker with a 1-year history of COPD with a positive outcome. The patient suffered from severe respiratory failure, requiring the use of ventilation gave 2 L/min oxygen on pressure control ventilation mode. Our findings suggest that the development of COVID-19, which could lead to death, needs critical assessment and special consideration for COPD patients and existing smokers.
Hypertensive disorders of pregnancy increase the risk of future menopausal hot flashes in Japanese women: results from the Japan Nurses’ Health Study
Authors: Ri Moyo , Hayashi Kunihiko , Kurabayashi Takumi , Lee Jung Su , Ideno Yuki , Nagai Kazue , Yasui Toshiyuki , Kubota Toshihiro , Takamatsu Kiyoshi
Published: October 2021

Objective:

We aimed to investigate whether hypertensive disorders of pregnancy (HDP) are associated with problematic hot flashes in Japanese women.

Methods:

In this study, we included participants in the Japan Nurses’ Health Study who were women aged 41 to 55 years at baseline, parous, and completed a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology.

Results:

At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of HDP. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of HDP of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with HDP as compared with those without these disorders.

Conclusions:

In this prospective study, we found that women with a history of HDP have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of HDP.
Optimizing the ocular surface prior to cataract surgery
Authors: He Xu , Huang Andy S. , Jeng Bennie H.
Published: October 2021

Purpose of review

Ocular surface disease can significantly impact the outcomes of cataract surgery. Recent studies have examined the efficacy of several new dry eye disease (DED) therapies, the extent to which epithelial debridement affects keratometric measurements in epithelial basement membrane dystrophy (EBMD) and Salzmann nodular degeneration (SND), and the predictability of refractive error following combined pterygium and cataract removal. This review aims to incorporate these newer studies in updating and further emphasizing the need for careful management and optimization of common ocular surface conditions prior to cataract surgery.

Recent findings

Common ocular surface conditions such as DED, EBMD, SND, and pterygium can cause significant irregular astigmatism and higher-order aberrations. Their resolution can substantially alter biometry measurements in preparation for cataract surgery, affecting the final visual outcome. Newer therapies for DED, such as topical lifitegrast and thermal pulsation treatment, can aid in this optimization process. If superficial keratectomy or excisions of lesions on the ocular surface are performed, sufficient healing time is needed to allow the ocular surface to reach stability prior to biometry measurements.

Ocular surface optimization is key to successful cataract surgery planning and reaching desired outcomes.
Uveitis–glaucoma–hyphema syndrome after uneventful placement of a 1-piece intraocular lens into the capsular bag
Authors: Nath Siddharth , Rai Amandeep S.
Published: October 2021

Introduction:

Uveitis-glaucoma-hyphema (UGH) syndrome is an uncommon but serious complication of cataract surgery that occurs from chafing of the iris by an intraocular lens (IOL). UGH syndrome is typically associated with first-generation lenses, placement of an IOL in the ciliary sulcus, or bag-sulcus tilted positioning. UGH syndrome following placement of a modern 1-piece lens in the capsular bag is rare.

Patient and clinical findings:

A 55-year-old man presented with UGH syndrome 2 weeks after routine cataract surgery with in-the-bag placement of a contemporary IOL.

Diagnosis, intervention, and outcomes:

Correct positioning of the IOL was confirmed with ultrasound biomicroscopy and exploratory surgery, and IOL exchange achieved resolution of UGH sequelae.

Conclusions:

Intermittent chafing of the iris by the IOL as a result of underlying traumatic zonulopathy contributed to the development of UGH, and surgeons should be aware of this complication even with in-the-bag placement of a modern IOL.
Analgesic effect of ivabradine against inflammatory pain mediated by hyperpolarization-activated cyclic nucleotide–gated cation channels expressed on primary afferent terminals in the spinal dorsal horn
Authors: Ohashi Nobuko , Uta Daisuke , Ohashi Masayuki , Baba Hiroshi
Published: October 2021

Ivabradine, a hyperpolarization-activated cyclic nucleotide–gated cation (HCN) channel blocker and clinically approved bradycardic agent, has analgesic effects against neuropathic pain. Although the expression of HCN channels in the spinal dorsal horn (SDH) is augmented under inflammatory pain, spinal responses to centrally and peripherally applied ivabradine remain poorly understood. We investigated the spinal action and cellular mechanisms underlying the drug's analgesic effects against inflammatory pain using inflammatory pain model rats. Intraperitoneal and intrathecal injections of ivabradine inhibited mechanical allodynia (6 rats/dose; P < 0.05), and immunohistochemical staining showed that ivabradine suppresses the phosphorylated extracellular signal–regulated kinase activation in the SDH (6 rats/group, P < 0.01). In vitro whole-cell patch-clamp and in vivo extracellular recordings showed that direct application of ivabradine to the spinal cord decreases the mean miniature excitatory postsynaptic currents' frequency (13 rats; P < 0.01), and direct and peripheral application of ivabradine suppresses the spinal response to mechanical stimulation–evoked firing (8 rats/group, P < 0.01). Moreover, ivabradine reduces the amplitudes of monosynaptic excitatory postsynaptic currents evoked by Aδ-fiber and C-fiber stimulation (6 rats; P < 0.01) and induces a stronger inhibition of those evoked by C-fiber stimulation. These phenomena were inhibited by forskolin, an activator of HCN channels. In conclusion, spinal responses mediated by HCN channels on primary afferent terminals are suppressed by central and peripheral administration of ivabradine; the drug also exhibits analgesic effects against inflammatory pain. In addition, ivabradine preferentially acts on C-fiber terminals of SDH neurons and induces a stronger inhibition of neuronal excitability in inflammatory pain.
Comparing paclitaxel-platinum with ifosfamide-platinum as the front-line chemotherapy for patients with advanced-stage uterine carcinosarcoma
Authors: Su Ming-Hsuan , Wu Hua-Hsi , Huang Hsin-Yi , Lee Na-Rong , Chang Wen-Hsun , Lin Shih-Chieh , Chen Yi-Jen , Wang Peng-Hui
Published: October 2021

Background:

Uterine carcinosarcoma (UCS) is a rare but highly lethal disease. Adjuvant chemotherapy is highly recommended for advanced UCS. To date, the standard chemotherapy regimen is still uncertain, although two regimens as paclitaxel-platinum (PP) and ifosfamide-platinum (IP) regimens are most commonly used. The aims of the current study attempt to compare both regimens in the management of advanced UCS patients.

Methods:

We evaluated advanced UCS patients who were treated either with PP or with IP after primary cytoreductive surgery in single institute retrospectively. The clinical-pathological parameters, recurrence, and survival were recorded.

Results:

A total of 16 patients were analyzed. Twelve patients received adjuvant PP therapy, and the remaining four patients received IP therapy. The median follow-up time was 28 months, ranging from 3.8 months to 121 months. Disease-related death occurred in 10 patients (62.5%). The median progression-free survival was 4.9 months, ranging from 3.8 months to 36.5 months in IP, and 23.1 months, ranging from 9.3 months to 121 months in PP, with statistically significant difference (p = 0.04). The median overall survival was 9.5 months (ranging from 3.8 months to 36.5 months) and 28.7 months (ranging from 10.3 months to 121 months) in IP and PP, respectively, without statistically significant difference (p = 0.06). Presence of pelvic and para-aortic lymphadenopathy and deep myometrial invasion (>1/2) were associated with worse prognosis by univariate analysis. No prognostic factor could be identified using multivariate analysis model.

Conclusion:

In the current study, due to extremely little number of subjects enrolled, the advantage of using paclitaxel-platinum regimen in the management of advanced UCS was still unclear, although a certain trend of favoring was supposed. We are looking forward to seeing more studies to identify the approximate regimen in the management of this highly lethal disease.
Characterization of Postural Sway in Patients With Persistent Postural-Perceptual Dizziness (PPPD) Using Wearable Motion Sensors
Authors: McCaslin Devin L. , Shepard Neil T. , Hollman John H. , Staab Jeffrey P.
Published: October 2021

Objective:

To extend previous investigations of postural control in patients with persistent-postural perceptual dizziness (PPPD).

Study Design:

Case-controlled, cross-sectional, observational investigation.

Setting:

Tertiary care center.

Patients:

Fifteen patients with PPPD, 15 control volunteers.

Interventions:

Measurement of anterior-posterior (AP) and medial-lateral (ML) sway at the waist using wearable accelerometers during posturography; assessment of reach and gait.

Main Outcome Measures:

Peak-to-peak AP and ML sway displacement on the six conditions of the Sensory Organization Test (SOT); Scores on the SOT, Functional Reach Test (FRT), and Dynamic Gait Index (DGI).

Results:

Compared to control volunteers, patients with PPPD had significantly greater sway displacement at the waist in the AP direction in SOT conditions 3, 5, and 6 and in the ML direction in SOT conditions 2 and 4, resulting in significantly lower median equilibrium scores on the composite index and all six SOT conditions. Patients with PPPD had significantly lower scores on the FRT and DGI that were not correlated with SOT performance. AP sway in conditions 3 and 6 differentiated patients with PPPD from controls with high sensitivity (≥0.87) and specificity (≥0.87).

Conclusions:

This study replicated previous work showing poor SOT performance by patients with PPPD who had greater AP sway associated with visual dependence and greater ML sway in low demand conditions than controls. Patients with PPPD also performed poorer on the FRT and DGI, but lack of correlation with SOT scores suggested different mechanisms of impairment in postural control, reach, and ambulation. AP sway demonstrated potential as a diagnostic marker.
The Plane of Mesh Placement Does Not Impact Abdominal Donor Site Complications in Microsurgical Breast Reconstruction
Authors: Henn Dominic , Sivaraj Dharshan , Barrera Janos A. , Lin John Q. , Chattopadhyay Arhana , Maan Zeshaan N. , Chen Kellen , Nguyen Alan , Cheesborough Jennifer , Gurtner Geoffrey C. , Lee Gordon K. , Nazerali Rahim
Published: October 2021

Background

Reinforcement of the abdominal wall with synthetic mesh in autologous breast reconstruction using abdominal free tissue transfer decreases the risk of bulging and herniation. However, the impact of the plane of mesh placement on donor site complications has not yet been investigated.

Methods

We performed a retrospective analysis of 312 patients who had undergone autologous breast reconstruction with muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps or deep inferior epigastric perforator (DIEP) flaps as well as polypropylene mesh implantation at the donor site. Donor site complications were compared among patients with different flap types and different mesh positions including overlay (n = 90), inlay and overlay (I-O; n = 134), and sublay (n = 88).

Results

Abdominal hernias occurred in 2.86% of patients who had undergone MS-TRAM reconstructions and in 2.63% of patients who had undergone DIEP reconstructions. When comparing patients with different mesh positions, donor site complications occurred in 14.4% of patients with overlay mesh, 13.4% of patients with I-O mesh, and 10.2% of patients with sublay mesh (P = 0.68). Abdominal hernias occurred in 4.44% of patients with overlay mesh, 2.24% of patients with I-O mesh, and 2.27% of patients with sublay mesh (P = 0.69). Multivariable logistic regression analysis did not identify a significant association between mesh position and hernia rates as well as wound complications.

Conclusions

Our data indicate that the plane of synthetic mesh placement in relation to the rectus abdominis muscle does not impact the rate of postoperative donor site complications in patients undergoing breast reconstruction with MS-TRAM or DIEP flaps.
A shark's eye view: testing the ‘mistaken identity theory’ behind shark bites on humans
Authors: Ryan Laura A. , Slip David J. , Chapuis Lucille , Collin Shaun P. , Gennari Enrico , Hemmi Jan M. , How Martin J. , Huveneers Charlie , Peddemors Victor M. , Tosetto Louise , Hart Nathan S.
Published: October 2021

Shark bites on humans are rare but are sufficiently frequent to generate substantial public concern, which typically leads to measures to reduce their frequency. Unfortunately, we understand little about why sharks bite humans. One theory for bites occurring at the surface, e.g. on surfers, is that of mistaken identity, whereby sharks mistake humans for their typical prey (pinnipeds in the case of white sharks). This study tests the mistaken identity theory by comparing video footage of pinnipeds, humans swimming and humans paddling surfboards, from the perspective of a white shark viewing these objects from below. Videos were processed to reflect how a shark's retina would detect the visual motion and shape cues. Motion cues of humans swimming, humans paddling surfboards and pinnipeds swimming did not differ significantly. The shape of paddled surfboards and human swimmers was also similar to that of pinnipeds with their flippers abducted. The difference in shape between pinnipeds with abducted versus adducted flippers was bigger than between pinnipeds with flippers abducted and surfboards or human swimmers. From the perspective of a white shark, therefore, neither visual motion nor shape cues allow an unequivocal visual distinction between pinnipeds and humans, supporting the mistaken identity theory behind some bites.
Differential nasopharyngeal microbiota composition in children according to respiratory health status
Authors: Henares Desiree , Brotons Pedro , de Sevilla Mariona F. , Fernandez-Lopez Ana , Hernandez-Bou Susanna , Perez-Argüello Amaresh , Mira Alex , Muñoz-Almagro Carmen , Cabrera-Rubio Raul
Published: October 2021

Acute respiratory infections (ARIs) constitute one of the leading causes of antibiotic administration, hospitalization and death among children <5 years old. The upper respiratory tract microbiota has been suggested to explain differential susceptibility to ARIs and modulate ARI severity. The aim of the present study was to investigate the relation of nasopharyngeal microbiota and other microbiological parameters with respiratory health and disease, and to assess nasopharyngeal microbiota diagnostic utility for discriminating between different respiratory health statuses. We conducted a prospective case–control study at Hospital Sant Joan de Deu (Barcelona, Spain) from 2014 to 2018. This study included three groups of children <18 years with gradual decrease of ARI severity: cases with invasive pneumococcal disease (IPD) (representative of lower respiratory tract infections and systemic infections), symptomatic controls with mild viral upper respiratory tract infections (URTI), and healthy/asymptomatic controls according to an approximate case–control ratio 1:2. Nasopharyngeal samples were collected from participants for detection, quantification and serotyping of pneumococcal DNA, viral DNA/RNA detection and 16S rRNA gene sequencing. Microbiological parameters were included on case–control classification models. A total of 140 subjects were recruited (IPD=27, URTI=48, healthy/asymptomatic control=65). Children’s nasopharyngeal microbiota composition varied according to respiratory health status and infection severity. The IPD group was characterized by overrepresentation of

Streptococcus pneumoniae

, higher frequency of invasive pneumococcal serotypes, increased rate of viral infection and underrepresentation of potential protective bacterial species such as

Dolosigranulum pigrum

and

Moraxella lincolnii

. Microbiota-based classification models differentiated cases from controls with moderately high accuracy. These results demonstrate the close relationship existing between a child’s nasopharyngeal microbiota and respiratory health, and provide initial evidence of the potential of microbiota-based diagnostics for differential diagnosis of severe ARIs using non-invasive samples.
Interrogation of T Cell-Enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism
Authors: Harbison R. Alex , Pandey Rajeev , Considine Michael , Leone Robert D. , Murray-Stewart Tracy , Erbe Rossin , Mandal Raj , Burns Mark , Casero Robert , Seiwert Tanguy , Fakhry Carole , Pardoll Drew , Fertig Elana , Powell Jonathan D.
Published: October 2021

Background

The presence of cytotoxic tumor infiltrating lymphocytes (TILs) and antigen (e.g., viral, tumor neoantigens) enhances anti-tumor immunity. However, features including recruitment of tolerogenic cell types, nutrient-depletion, and the establishment of an acidic and hypoxic microenvironment diminish anti-tumor lymphocyte function. We sought to understand why the anti-tumor immune response fails despite a favorable immune profile.

Methods

We leveraged human papillomavirus-related (HPV+) head and neck squamous cell carcinomas (HNSC) to address this question given their high degree of CD8+ T cell-infiltration and virus-derived tumor-associated antigens. We evaluated expression of 2,520 metabolic genes between HPV+ HNSCs of different prognostic phenotypes. We further tested tumor-intrinsic and -extrinsic sources of polyamine (PA) gene expression based on observations from the prior analysis. We used bulk RNAseq from The Cancer Genome Atlas (TCGA; 10 different cancers) and single cell (sc) RNAseq data from two atlases to parse immune cell contributions to polyamine gene expression. We used TCGA data and an immunotherapy-treated melanoma cohort to examine survival outcomes as a function of polyamine gene set expression.

Results

PA metabolism genes were upregulated in aggressive phenotype, T cell-enriched (Thi), HPV+ HNSCs. PA synthesis and transporter gene enrichment was associated with T cell infiltration, recurrent or persistent cancer, overall survival status, primary site, molecular subtype, and MYC genomic alterations. PA synthesis and transport gene sets were more highly expressed in HPV-compared to HPV+ HNSCs. Bulk and scRNAseq data from HPV+ HNSCs demonstrated greater PA catabolism gene set expression among myeloid cells. A combined PA gene set comprised of genes involved in PA synthesis and transport was negatively correlated with cytotoxic T cell functional score across TCGA tumor types. Combined PA gene set expression was associated with greater mortality risk across five tumor types and worse survival in T cell-infiltrated, anti-PD-1-treated melanomas.

Conclusions

A genomic approach leveraging T cell-infiltrated, immunogenic HPV+ HNSCs revealed an association between polyamine metabolism, anti-tumor immunity, and prognosis across several cancer types. These data address hurdles to anti-tumor immunity and immunotherapy and warrant further investigation of polyamines as a biomarker for targeted therapy in the context of a T cell-infiltrated microenvironment.
Effect of the foot-strike pattern on temporal characteristics of sagittal plane knee kinetics and kinematics during the early phase of cutting movements
Authors: Uno Yuki , Ogasawara Issei , Konda Shoji , Wakabayashi Kaito , Motoi Miyakawa , Nambo Megumi , Umegaki Kaho , Cheng Haotian , Hashizume Ken , Nakata Ken
Published: October 2021

Anterior cruciate ligament (ACL) injury occurs soon after foot-strike. Cutting with a shallow flexed knee is considered a risk factor for ACL injury; however, how foot-strike patterns (forefoot strike [FFS] vs. rearfoot strike [RFS]) affect sagittal plane knee kinetics and kinematics after a foot-strike, is unknown. This study aimed to investigate the effect of foot-strike patterns on the temporal characteristics in sagittal plane knee kinetics and kinematics during cutting. Twenty-three males performed 45° cutting under RFS and FFS conditions. The marker position data on the lower limb, and the ground reaction force (GRF) data were collected and time-normalized (0%–100%) during the stance phase. The knee flexion angle, shank and GRF vector inclination angle relative to the global vertical axis, knee flexion/extension moment, and anterior/posterior component of GRF relative to the shank segment were calculated and compared between foot-strike patterns using statistical parametric mapping paired t-test (p<0.0071). The knee flexion angle was smaller in the RFS than in the FFS in the initial 40% of the stance phase. In the RFS condition, the GRF vector was directed anteriorly to the shank segment, and the knee extension moment was produced by GRF in 0%– 7% of the stance phase; these results were not observed in the FFS condition. These results suggest that compared to FFS, RFS induces a shallow flexed knee with an anterior-directed GRF component in the early stance phase, and might potentially provoke a risk of ACL injury.

Highlights

Sagittal plane knee mechanics differed between foot-strike patterns.

Shallower knee flexion occurred in rearfoot strike than in forefoot strike in cutting.

Ground reaction force vector directed anteriorly to shank axis in rearfoot strike.

Larger Knee extension moment occurred after initial contact in rearfoot strike.

Rearfoot strike had a potentially higher risk for ACL injury than forefoot strike.
APOEmissense variant R145C is associated with increased Alzheimer’s disease risk in African ancestry individuals with theAPOE ε3/ε4genotype
Authors: Guen Yann Le , Belloy Michael E. , Eger Sarah J. , Chen Annabel , Kennedy Gabriel , Thornton Timothy A. , Farrer Lindsay A. , Napolioni Valerio , He Zihuai , Greicius Michael D.
Published: October 2021

BACKGROUND

TheAPOEgene has two common missense variants that greatly impact the risk of late-onset Alzheimer’s disease (AD). Here we examined the risk of a thirdAPOEmissense variant, R145C, that is rare in European-Americans but present in 4% of African-Americans and always in phase withAPOE ε3.

METHODS

In this study, we included 11,790 individuals of African and Admixed-African ancestry (4,089 cases and 7,701 controls). The discovery sample was composed of next generation sequencing data (2,888 cases and 4,957 controls), and the replication was composed of microarray data imputed on the TOPMed reference panel (1,201 cases and 2,744 contols). To assess the effect of R145C independently of theε2andε4alleles, we performed stratified analyses inε2/ε3, ε3/ε3, andε3/ε4subjects. In primary analyses, the AD risk associated with R145C was estimated using a linear mixed model regression on case-control diagnosis. In secondary analyses, we estimated the influence of R145C on age-at-onset using linear-mixed-model regression, and risk of conversion to AD using competing risk regression.

RESULTS

Inε3/ε4-stratified meta-analyses, R145C carriers had an almost three-fold increased risk compared to non-carriers (odds ratio, 2.75; 95% confidence interval [CI], 1.84 to 4.11; P = 8.3×10−7) and had a reported AD age-at-onset almost 6 years younger (β, -5.72; 95% CI, 7.87 to -3.56; P = 2.0×10−7). Competing risk regression showed that the cumulative incidence of AD grows faster with age in R145C carriers compared to non-carriers (hazard ratio, 2.42, 95% CI, 1.81 to 3.25; P = 3.7×10−9).

CONCLUSION

The R145C variant is a potent risk factor for AD among African ancestry individuals with theε3/ε4genotype. Our findings should enhance AD risk prediction in African ancestry individuals and help elucidate the mechanisms linking the apoE protein to AD pathogenesis. The findings also add to the growing body of evidence demonstrating the importance of including ancestrally-diverse populations in genetic studies.
Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort
Authors: Spurny-Dworak B , Handschuh P , Spies M , Kaufmann U , Seiger R , Klöbl M , Konadu ME , Reed MB , Ritter V , Baldinger-Melich P , Bogner W , Kranz GS , Lanzenberger R
Published: October 2021

Sex hormones affect the GABAergic and glutamatergic neurotransmitter system as demonstrated in animal studies. However, human research has mostly been correlational in nature. Here, we aimed at substantiating causal interpretations of the interaction between sex hormones and neurotransmitter function by using magnetic resonance spectroscopy imaging (MRSI) to study the effect of gender-affirming hormone treatment (GHT) in transgender individuals.

Fifteen trans men (TM) with a DSM-5 diagnosis of gender dysphoria, and 15 age-matched cisgender women (CW) underwent MRSI before and after at least 12 weeks of GHT. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (a combination of GABA and macromolecules) and Glx (a combination of glutamate and glutamine) ratios to total creatine (GABA+/tCr, Glx/tCr) were calculated in five predefined regions-of-interest (hippocampus, insula, pallidum, putamen and thalamus).

Linear mixed models analysis revealed a significant measurement by gender identity effect (pcorr. = 0.048) for GABA+/tCr ratios in the hippocampus, with the TM cohort showing decreased GABA+/tCr levels after GHT compared to CW. Moreover, analysis of covariance showed a significant sex difference in insula GABA+/tCr ratios (pcorr. = 0.049), indicating elevated GABA levels in cisgender women compared to cisgender men.

Our study demonstrates GHT treatment-induced GABA+/tCr reductions in the hippocampus, indicating hormone receptor activation on GABAergic cells and testosterone-induced neuroplastic processes within the hippocampus. Moreover, elevated GABA levels in the female compared to the male insula highlight the importance of including sex as factor in future MRS studies.
Leveraging machine learning and self-administered tests to predict COVID-19: An olfactory and gustatory dysfunction assessment through crowd-sourced data in India
Authors: Kumar Ritesh , Singh Maneet , Singh Prateek , Parma Valentina , Ohla Kathrin , Olsson Shannon B , Saini Varun , Rani Jyotsna , Kishore Kunal , Kumari Priyanka , Ichhpujani Parul , Sharma Anupma , Kumar Saurav , Sharma Manu , Bhondekar Amol P , Kothari Anamika , Sardana Viren , Iyengar Sudarshan , Dash Debasis , Kaur Rishemjit
Published: October 2021

It has been established that smell and taste loss are frequent symptoms during COVID-19 onset. Most evidence stems from medical exams or self-reports. The latter is particularly confounded by the common confusion of smell and taste. Here, we tested whether practical smelling and tasting with household items can be used to assess smell and taste loss. We conducted an online survey and asked participants to use common household items to perform a smell and taste test. We also acquired generic information on demographics, health issues including COVID-19 diagnosis, and current symptoms. We developed several machine learning models to predict COVID-19 diagnosis. We found that the random forest classifier consistently performed better than other models like support vector machines or logistic regression. The smell and taste perception of self-administered household items were statistically different for COVID-19 positive and negative participants. The most frequently selected items that also discriminated between COVID-19 positive and negative participants were clove, coriander seeds, and coffee for smell and salt, lemon juice, and chillies for taste. Our study shows that the results of smelling and tasting household items can be used to predict COVID-19 illness and highlight the potential of a simple home-test to help identify the infection and prevent the spread.