bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of Chromatographic Method for the Standardization of Homeopathic Formulation of Syzygium Cumini
Authors: Mishra Rashmi , Kotagale Nandakishor , Umekar Milind , Sahu Rajesh , Maliye Amit , Gurav Shailendra
Published: May 2021

Background Syzygium cumini (Lam.), family Myrtaceae, has a long history of use in folk and traditional systems of indigenous medicine. Many homeopathic formulations of Jamun seeds are available in the market for their crucial usage as an anti-diabetic. Despite the popularity of homeopathic products, a lack of standard quality is a significant impediment in their acceptance. The present study aimed to develop and validate a chromatographic method for the standardization of the homeopathic formulation of Syzygium cumini.

Methods The seeds of Syzygium cumini were studied for physicochemical evaluation and preliminary phytochemical screening. Also, the in-house standard and marketed homeopathic formulations of Syzigium cumini were standardized for pH, total fatty content, total phenolic and flavonoid content, with quantitative high-performance liquid chromatography- photodiode array detector (HPLC-PDA) analysis by using ellagic acid as a marker.

Results The physicochemical characteristics of crude material were found to be within pharmacopeial limits. The phytochemical screening showed the presence of various secondary metabolites. The total phenolic and flavonoid content was higher in the in-house standard than in marketed formulations. A validated quantitative HPLC-PDA analysis showed variations of ellagic acid content in different homeopathic formulations.

Conclusion Physicochemical analysis and the HPLC method for quantitative estimation of ellagic acid can be used to standardize a homeopathic formulation of Syzygium cumini.
GRIN2A and GRIN2B and Their Related Phenotypes
Authors: Sapuppo Annamaria , Portale Laura , Massimino Carmela R. , Presti Santiago , Tardino Lucia , Marino Simona , Polizzi Agata , Falsaperla Raffaele , Praticò Andrea D.
Published: May 2021

Glutamate is the most relevant excitatory neurotransmitter of the central nervous system; it binds with several receptors, including N-methyl-D-aspartate receptors (NMDARs), a subtype of ionotropic glutamate receptor that displays voltage-dependent block by Mg2+ and a high permeability to Ca2+. GRIN2A and GRIN2B genes encode the GluN2A and GluN2B subunits of the NMDARs, which play important roles in synaptogenesis, synaptic transmission, and synaptic plasticity, as well as contributing to neuronal loss and dysfunction in several neurological disorders. Recently, individuals with a range of childhood-onset drug-resistant epilepsies, such as Landau–Kleffner or Lennox–Gastaut syndrome, intellectual disability (ID), and other neurodevelopmental abnormalities have been found to carry mutations in GRIN2A and GRIN2B, with high variable expressivity in phenotype. The first one is found mainly in epilepsy-aphasia syndromes, while the second one mainly in autism, schizophrenia, and ID, such as autism spectrum disorders. Brain magnetic resonance imaging alterations are found in some patients, even if without a clear clinical correlation. At the same time, increasing data on genotype–phenotype correlation have been found, but this is still not fully demonstrated. There are no specific therapies for the treatment of correlated NMDARs epilepsy, although some evidence with memantine, an antagonist of glutamate receptor, is reported in the literature in selected cases with mutation determining a gain of function.
FOXG1 Gene and Its Related Phenotypes
Authors: Pecora Giulia , Sortino Vincenzo , Brafa Musicoro Viviana , Salomone Giulia , Pizzo Francesco , Costanza Giuseppe , Falsaperla Raffaele , Zanghì Antonio , Praticò Andrea D.
Published: May 2021

FOXG1 is an important transcriptional repressor found in cell precursor of the ventricular region and in neurons in the early stage of differentiation during the development of the nervous epithelium in the cerebrum and optical formation. Mutations involving FOXG1 gene have been described first in subjects with congenital Rett syndrome. They can cause seizure, delayed psychomotor development, language disorders, and autism. FOXG1 deletions or intragenic mutations also determinate reduction in head circumference, structural defects in the corpus callosum, abnormal movements, especially choreiform, and intellectual retardation with no speech. Patients with duplications of 14q12 present infantile spasms and have subsequent intellectual disability with autistic features, head circumference in the normal range, and regular aspect of corpus callosum. Clinical characteristics of patients with FOXG1 variants include growth deficit after birth associated with microcephaly, facial dysmorphisms, important delay with no language, deficit in social interaction like autism, sleep disorders, stereotypes, including dyskinesia, and seizures. In these patients, it is not characteristic a history of loss of acquired skills.
PCDH19-Related Epilepsies
Authors: Mazzurco Marina , Pulvirenti Giulio , Caccamo Martina , Presti Santiago , Soma Rachele , Salafia Stefania , Praticò Elena R. , Filosco Federica , Falsaperla Raffaele , Praticò Andrea D.
Published: May 2021

Protocadherin-19 (PCDH19) is considered one of the most relevant genes related to epilepsy. To date, more than 150 mutations have been identified as causative for PCDH19-female epilepsy (also known as early infantile epileptic encephalopathy-9, EIEE9), which is characterized by early onset epilepsy, intellectual disabilities, and behavioral disturbances. More recently, mosaic-males (i.e., exhibiting the variants in less than 25% of their cells) have been described as affected by infant-onset epilepsy associated with intellectual disability, as well as compulsive or aggressive behavior and autistic features. Although little is known about the physiological role of PCDH19 protein and the pathogenic mechanisms that lead to EIEE9, many reports and clinical observation seem to suggest a relevant role of this protein in the development of cellular hyperexcitability. However, a genotype–phenotype correlation is difficult to establish. The main feature of EIEE9 consists in early onset of seizures, which generally occur in clusters lasting 1 to 5 minutes and repeating up to 10 times a day for several days. Seizures tend to present during febrile episodes, similarly to the first phases of Dravet syndrome and PCDH19 variants have been found in ∼25% of females who present with features of Dravet syndrome and testing negative for SCN1A variants. There is no “standardized” treatment for PCDH19-related epilepsy and most of the patients receiving a combination of several drugs. In this review, we focus on the latest researches on these aspects, with regard to protein expression, its known functions, and the mechanisms by which the protein acts. The clinical phenotypes related to PCDH19 mutations are also discussed.
PRRT2 Related Epilepsies: A Gene Review
Authors: Massimino Carmela Rita , Portale Laura , Sapuppo Annamaria , Pizzo Francesco , Sciuto Laura , Romano Catia , Salafia Stefania , Falsaperla Raffaele
Published: May 2021

PRRT2 encodes for proline-rich transmembrane protein 2 involved in synaptic vesicle fusion and presynaptic neurotransmitter release. Mutations in human PRRT2 have been related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with choreoathetosis, benign familial infantile epilepsies, and hemiplegic migraine. PRRT2 mutations cause neuronal hyperexcitability, which could be related to basal ganglia or cortical circuits dysfunction, leading to paroxysmal disorders. PRRT2 is expressed in the cerebral cortex, basal ganglia, and cerebellum. Approximately, 90% of pathogenic variants are inherited and 10% are de novo. Paroxysmal attacks in PKD are characterized by dystonia, choreoathetosis, and ballismus. In the benign familial infantile epilepsy (BFIE), seizures are usually focal with or without generalization, usually begin between 3 and 12 months of age and remit by 2 years of age. In 30% of cases of PRRT2-associated PKD, there is an association with BFIE, and this entity is referred to as PKD with infantile convulsions (PKD/IC). PRRT2 mutations are the cause of benign family childhood epilepsy and PKD/IC. On the other hand, PRRT2 mutations do not seem to correlate with other types of epilepsy. The increasing incidence of hemiplegic migraine in families with PRRT2-associated PKD or PKD/IC suggests a common disease pathway, and it is possible to assert that BFIE, paroxysmal kinesigenic dyskinesia, and PKD with IC belong to a continuous disease spectrum of PRRT2-associated diseases.
Supera Stent Implantation with Ultrasound Guidance for Complex Ostial Lesions of Superficial Femoral Artery by Retrograde Approach: The SUGAR Technique
Authors: Sheorain Virender Singh , Parakh Rajiv , Grover Tarun , Sahu Tapish , Aher Ashutosh
Published: May 2021

Purpose The aim of this study was to describe a modified technique for accurate deployment of the Supera stent under ultrasound (US) guidance for complex lesions involving superficial femoral artery (SFA) ostium without jailing profunda femoral artery (PFA) by retrograde approach.

Technique Retrograde pedal access was initially taken in all the cases. The stenotic or occlusive femoropopliteal lesions involving the SFA ostium were crossed retrogradely and additional contralateral common femoral artery (CFA) access was taken only if we failed to cross the lesion. In addition to fluoroscopy, extravascular US guidance was freely used whenever required throughout the procedure. After desired predilatation of the SFA lesion, US guidance (gray scale and color Doppler) was used to start deployment of the proximal few centimeters of Supera stent ensuring that the landing of first crown was exactly from the SFA ostium not extending into CFA or jailing the PFA ostium. The rest of the stent was deployed under fluoroscopic guidance. Retrograde pedal access site hemostasis was achieved by manual compression. The Supera stent implantation with Ultrasound Guidance for complex ostial lesions of superficial femoral Artery by Retrograde approach (SUGAR) technique was applied successfully in 35 patients (mean age 58.1 ± 4.4 years; 24 males) with critical limb ischemia via the distal pedal approach. No access site or remote complications were observed.

Conclusion The SUGAR technique has superior advantage of utilizing a simple tool like extravascular US in addition to fluoroscopy for retrograde Supera stent deployment by allowing very precise landing at SFA ostium, bypassing the need for multiple oblique projections, unwanted radiation exposure, and extra contrast dye overload.
A questionnaire-based study of impersonalization in Romanian and English
Authors: Rădulescu Valentin , Van Olmen Daniël
Published: May 2021

This paper is the first contrastive study of impersonalization in Romanian and English. Taking an acceptability judgment approach, we describe the functional potential in all impersonal uses of not only the pronouns ‘one’, ‘you’ and ‘they’ but also the lesser studied passive. We find inter alia: a similar division of labor in the languages between ‘you’ and ‘they’ for contexts paraphrasable as, respectively, ‘everyone’ and ‘someone/some people’; a wider range of uses for pro-dropped ‘they’ than for its overt counterpart, as hypothesized in previous research; and a preference in English, but not Romanian, for passives to ‘they’ especially in contexts like ‘they’ve stolen my wallet!’, where the referent is entirely unidentifiable and likely to be singular. Levels of identifiability and number, each of which has been suggested in a separate semantic map as necessary for capturing impersonalization, are also shown to interact, supporting a proposal to combine them in one map.
A phonological investigation of Sanzari Boro
Authors: Mahela Ratul , Sinha Sweta
Published: May 2021

This study attempts to investigate the phonological structures of Sanzari Boro (SB), a variety of Boro, a
Tibeto-Burman language that is mainly spoken in the state of Assam in the North East India. This paper highlights the phonological
processes in SB that have emerged due to geographical as well as social factors and language contact. This research is based on
the data collected from 10 native speakers. The analysis of data reveals that although Standard Boro and SB have similarities in
some features, they contain some evident differences too. A closer investigation of data establishes that SB has maximum number of
phonemes as compared to any other variety of Boro and it has three distinct tones that have been observed in monosyllabic words.
Declustering is facilitated through epenthesis. Phonological processes like deletion, insertion, assimilation, weakening and
strengthening, metathesis and substitution are operational in formation of SB words.
Phenacoccus solenopsis (cotton mealybug).
Authors: Lambdin Paris
Published: May 2021

This mealybug species has the ability to increase rapidly in population size and spread to cover vast areas where host plants occur, in a relatively short period of time. It has been reported from over 200 hosts. Since the original description of P. solenopsis from Atriplex canescens in New Mexico, USA in 1898, no reports on its presence were reported until 1967 (McKenzie, 1967; McDaniel, 1975). Later, Fuchs et al. (1991) reported small, sporadic populations on cotton in Runnels County, Texas, USA in 1988 that spread 75 to 200 miles from the original site with contiguous populations by 1990. With the increase in international trade over the last few decades, this invasive pest has been collected and identified on host material at international ports and in greenhouses outside its native range (Jansen, 2004). As such, P. solenopsis has become established in the Afrotropical, Australasian, Nearctic, Neotropical, and Oriental regions.
Limnocharis flava (yellow bur-head).
Authors: Man Azmi
Published: May 2021

L. flava, commonly known as yellow bur head, is a perennial broad-leaved weed which behaves as an annual in certain habitats. It spreads throughout South-East Asia especially in rice crops, and also in South America and the USA. It prefers wet conditions such as lowland rice fields, shallow canals and ditches and reproduces both by seed and vegetatively. Heavy infestations of L. flava indicate a fertile soil. The effectiveness of drainage ditches and irrigation channels can be reduced through siltation caused by blockages of L. flava leaves and roots. Young leaves, petioles and flower stalks can be eaten as vegetables. Whole plants are used as fodder for pigs, cattle or fish and plant residues can be also be used for feed and as green manure. L. flava can be controlled by chemical such as 2,4-D herbicides and sulfonyl urea products such as bensulfuron and bensulfuron/metsulfuron. Bentazon/MCPA can be used to control multiple resistant biotype of L. flava.
Linepithema humile (Argentine ant).
Authors: Gómez Crisanto , Abril Silvia
Published: May 2021

L. humile is one of the most invasive and problematic ant species in the world according to the Invasive Species Specialist Group (www.issg.org/database). Native to South America, it has spread worldwide in areas with Mediterranean-type climates usually associated with disturbed habitats as a result of human commercial activities. Its capacity to tolerate a wide range of abiotic conditions, its generalist dietary requirements and its unicolonial organization, which lead to the formation of large supercolonies, allow the species to spread easily and occupy a wide range of areas. In these areas, L. humile has impacted native ant faunas leading to changes in arthropod communities, ant-vertebrate interactions and ant-plant relationships. Its presence has also had economic effects, such as damage to infrastructure, and negative effects on crops and plantations due to its mutualistic interactions with hemipterans, which can affect the growth and production of the host plant.
Maliarpha separatella (African white rice borer).
Authors: Beverley Claire
Published: May 2021

M. separatella is a stem borer of sub-Saharan and Indian Ocean islands and is the only rice stem borer that has widespread distribution in sub-Saharan Africa. Damage by M. separatella includes reduced plant height, total number of grains per panicle, number of filled grains per panicle and grain weight, depending on the plant stage attacked.
Microaggressions and Objectivity: Experimental Measures and Lived Experience
Authors: Akagi Mikio , Gooding Frederick W.
Published: May 2021

Microaggressions are, roughly, acts or states of affairs that express prejudice or neglect toward members of oppressed groups in relatively subtle ways. There is an apparent consensus among both proponents and critics of the microaggression concept that microaggressions are “subjective.” We examine what subjectivity amounts to in this context and argue against this consensus. We distinguish between microaggressions as an explanatory posit and microaggressions as a hermeneutical tool, arguing that in either case there is no reason at present to regard microaggressions as subjective and that microaggressions in the hermeneutical sense should be regarded as objective.
Effect of increasing the Al2O3 content on the phase formation and mechanical properties of lithium disilicate glass-ceramics
Authors: Leenakul Wilaiwan , Kraipok Arnon
Published: May 2021

Lithium disilicate glass ceramics with improved properties were prepared via a thermal treatment method by varying its composition. This study aims to investigate the influence of the concentration of Al2O3 additive oxides on the phase formation and mechanical properties of lithium disilicate glass ceramics prepared by conventional method. The Al2O3 concentration used are 3.0, 4.5, and 6.0 mol% for LCA1, LCA2, and LCA 3, respectively. As the content of Al2O3 increased the glass transition temperature (Tg), the crystallization temperature (Tc), phase formation, and mechanical properties of lithium disilicate glass ceramics varied considerably, demonstrating the substantial effect of Al2O3. After heat treatment at 600 °C and 800 °C for 1 h, the x-ray diffraction results showed that the major phase in all the glass-ceramic samples was Li2Si2O5 and the minor phases were CeO2, LiAlSi3O8, quartz, and Li2SiO3. For the lowest content of Al2O3, the highest flexural strength and Vickers hardness were obtained as 188.34 MPa and 776 HV, respectively. These results were attributed to the interlocking microstructure of rod-like Li2Si2O5 in the LCA1 sample.
A - 02 The Epidemiology of Concussion in Middle School Football
Authors: A Blackstone , P Kelshaw , S Hacherl , N Erdman , A Lincoln , R Dunn , J Martin , J Ambegaonkar , N Cortes , C McGill , S Caswell
Published: May 2021

Objective

Middle school is often the first exposure to American football for many children. However, research examining concussion in football has primarily focused on high school and older athletes. Therefore, we investigated the incidence of concussion and subsequent sport time loss (TL) in MS football.

Methods

Athlete exposure (AE) and injury rates (IR) were gathered by onsite Certified Athletic Trainers within public middle school for all events across the 2015/16–2019/20 school years. AE was defined as one athlete participating in one practice or game. TL was defined as the number of days between the injury and return to sport dates. Concussion rates per 1000AE with corresponding confidence intervals (CI) were calculated. Injury rate ratios (IRR) with 95% CIs were compared IR between practices and games. CIs excluding 1.0 were considered significant.

Results

75 concussions (IR = 1.38/1000AE, 95% CI = 1.06–1.69) occurred across 54,544 AEs. The concussion rate was significantly higher in games (n = 31, IR = 3.51, 95%CI = 2.27–4.75) than practices (n = 44, IR = 0.96, 95%CI = 0.68–1.25; IRR = 3.65, 95%CI = 2.30–5.77). The mean sport TL was 16.50 ± 8.25 days.

Conclusions

We observed middle school football concussion rates (practices and games) and associated TL from sport to be consistent with prior youth and high school football research. However, the concussion rate for middle school games was more than 3 times that of practices. This is similar to prior middle school football findings, but less than reported in high school football. Continued research evaluating modifiable risk factors for concussion in middle school football games and practices is needed.
A - 07 Post-Concussion Symptom Scale Factors Shift with Longer Time Since Injury in Adolescents with Sport-Related Concussion
Authors: SR Eagle , AM Kissinger-Knox , M Womble , RJ Elbin , Kegel N Feder A , M Collins , AP Kontos
Published: May 2021

Objective

To evaluate the role of time since injury on the factor structure of the Post-Concussion Symptom Scale (PCSS) for athletes after sustaining a sport-related concussion (SRC).

Methods

Adolescent athletes (n = 782) were dichotomized based on time since injury: 0–7 (EARLY; n = 321, age: 15.4 ± 1.9 years, 51.7% female), 8–14 (MIDDLE; n = 281, age: 15.8 ± 2.2 years, 54.8% female) and 15–30 days (LATE; n = 180, age: 15.6 ± 1.8 years, 52.8% female). An EFA was performed on the 22 variables of the PCSS for each of the three cohorts (primary factor loading of 0.6 to retain each item).

Results

EARLY had a five-component model (64% of total variance): 1) GLOBAL (18.0%; headache/dizziness/photosensitivity/phonosensitivity/difficulty concentrating), 2) FATIGUE/HYPERSOMNIA (16.4%; fatigue/drowsiness/mental fogginess/slowed down/hypersomnia), 3) AFFECTIVE (12.6%; more emotional/sadness), 4) INSOMNIA (9.0%; insomnia/trouble falling asleep), 5) SOMATIC (8.0%; vomiting/numbness). MIDDLE had a four-component model (63.1% of variance): 1) GLOBAL (19.4%; photosensitivity/headache/phonosensitivity/nausea/dizziness), 2) INSOMNIA/AFFECTIVE (14.4%; insomnia/more emotional/nervousness/trouble falling asleep), 3) SOMATIC/MEMORY (12.2%; difficulty remembering/numbness), and 4) HYPERSOMNIA (12.0%; drowsiness/hypersomnia). LATE had a four-component model (65.7% of variance): 1) VESTIBULAR/OCULAR (18.2%; vision/difficulty remembering/balance/fogginess/dizziness), 2) MIGRAINE (16.6%; photosensitivity/phonosensitivity/fatigue/headache), 3) AFFECTIVE (16.1%; sadness/nervousness/more emotional), and 4) INSOMNIA (7.6%; insomnia/trouble falling asleep).

Conclusions

The results of this study suggest greater time since injury modifies symptom factor structure in adolescent athletes with SRC. Specifically, symptom factors become more distinct with longer time since injury before first clinical visit. A GLOBAL symptom factor was observed for both EARLY and MIDDLE, but not in LATE. SOMATIC (i.e., numbness) was observed in EARLY/MIDDLE, but not LATE. Symptom factors in LATE seem to mirror concussion clinical sub-types from previous research (e.g., vestibular/ocular, migraine, affective, sleep).
A - 09 The Epidemiology of Concussion in Middle School Wrestling
Authors: SA Ferranti , PM Kelshaw , SL Hacherl , NK Erdman , AE Lincoln , RE Dunn , JR Martin , JP Ambegaonkar , N Cortes , C McGill , SV Caswell
Published: May 2021

Objective

Wrestling has among the highest concussion incidence in all high school and collegiate sports. Many children begin wrestling in middle school (MS), however, research describing concussion incidence in MS wrestling remains limited. Therefore, we sought to describe the incidence of concussion and subsequent sport time loss (TL) sustained by MS wrestlers.

Methods

Certified athletic trainers collected concussion and athlete exposure (AE) data for all MS wrestling practices and matches in a large metropolitan public-school division between 2015/16 and 2019/20. AE was defined as one athlete participating in one practice or match. Frequencies and proportions were calculated for diagnosed concussions by event type. TL was the number of days from date of injury to return to sport. Concussion injury rates (IR) per 1000 AEs and injury rate ratios (IRR) to compare IR between practice and matches were calculated with 95% Confidence Intervals (CIs). IRRs with 95% CIs excluding 1.0 were statistically significant.

Results

43 concussions occurred across 38,297 AEs (IR = 1.12, 95%CI = 0.79–1.46). No significant difference in the concussion IR between practices (n = 33, IR = 1.11, 95%CI = 0.73–1.49) and matches (n = 10, IR = 1.16, CI = 0.44–1.87; IRR = 1.04, 95% CI = 0.51–2.11) was observed. The mean TL was 18.38 ± 8.25 days.

Conclusions

We observed higher practice and match concussion rates than those previously reported among middle and high school wrestlers. Additionally, our findings showed that MS wrestlers required approximately 5 more days to return to sport than reported among HS wrestlers. Further investigation of concussion risk factors for concussion and prolonged TL in MS wrestling is needed.
A - 13 “Am I going to be like this forever?”: Athletes’ Experiences of Sport-Related Concussion Symptoms
Authors: CJ Kennedy , M Doucette , B Dupriez-Mitchell , MA Garcia-Barrera
Published: May 2021

Objective

Previous research has focused on understanding the symptoms and long-term effects of sport-related concussion (SRC) through quantitative methods. Less is known about the impacts of SRC from the athletes’ perspective. Therefore, the purpose of this study was to explore the lived experience of SRC symptoms among Canadian varsity athletes.

Methods

Semi-structured interviews were conducted via Zoom teleconferencing. Participants were 11 Canadian university varsity soccer and rugby athletes (M = 20.66 years, SD = 1.43 years; 45% female). All participants had experienced an SRC within the last 26 months. Thematic analysis was used to identify patterns across athletes’ experiences of SRC symptoms.

Results

Four unique themes emerged: (1) immediate disorientation, (2) prolonged emotional difficulties, (3) prolonged memory impairments and (4) executive dysfunction. Disorientation was the first SRC symptom experienced by 90% of athletes. Emotional disturbances were experienced throughout recovery with deficits in emotional regulation being the most salient for athletes. Difficulties with short-term and long-term memory were experienced by athletes up to 26 months post-SRC onset. Executive dysfunction manifested primarily as difficulties with planning and decision making. Lastly, long-term difficulties with speech articulation (e.g., stuttering and word-finding) were described as a unique symptom for a small subgroup (36%) of athletes.

Conclusions

Consistent with the literature, concussed athletes frequently described concerns about long-lasting symptoms and post-concussive difficulties with emotion, memory and executive function. Additional findings captured some nuance from the lived experience of post-concussion symptoms and their effect on athletes’ overall psychosocial functioning.
A - 22 Post-Concussive Changes in Menstrual Cycle Reporting: Comparing Self-Report Versus Blood Plasma Concentrations
Authors: S Ott , L Gonzalez , J Redell , J Duran , P Schatz , E Becker
Published: May 2021

Objective

Few studies have addressed serum levels of hypothalamic hormones, as a consequence of sports-related concussion, in concussed, female adolescent athletes.

Methods

Female athletes, ages 14–18, were assigned to two study groups: 1) 18 diagnosed with a sports-related concussion (SRC) and evaluated within 7 days of injury, and 2) 18 healthy participants matched on age, education, and sport. Participants self-reported menstrual cycle status, with Days 1–15 of the menstrual cycle corresponding to the Follicular phase and days >15 to the Luteal phase. Blood samples were drawn for Plasma concentration measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), adrenocorticotropin hormone (ACTH), prolactin, growth hormone (GH) and progesterone. Using progesterone plasma concentration, <=2 ng/mL corresponding to the Follicular phase and > 2 ng/mL corresponding to the Luteal phase.

Results

Across both groups, there was agreement between self-reported and progesterone plasma concentrations menstrual cycle Follicular (71.4%) or Luteal phase (52.9%) [X2(1) = 2.33, p = 0.13, phi = 0.25] in identifying menstrual cycle phases. Within the non-concussed controls, there was 90% agreement for Follicular phase and only 33.3% agreement for Luteal phase [X2(1) = 1.55, p = 0.30, phi = 0.29], and for the concussed athletes there was 54.5% agreement for Follicular phase and 75% agreement for Luteal phase [X2(1) = 1.66, p = 0.35, phi = 0.30]

Conclusions

We provide preliminary evidence of disruption of the hypothalamic–pituitary-axis (HPA) following mTBI as there was a 90% agreement between self-reported follicular phase and follicular phase determined by Progesterone levels for non-concussed females as compared to 54% agreement between the same measures for concussed females.
A - 26 AMPAR as a Sports Concussion Biomarker and Its Relationship to Neurocognitive Functioning in Collegiate Athletes
Authors: D Soden , J Maroon , W Selman , S Dambinova , G Izykenova , C Tangen , J Gunstad , S Briskin , S Miskovsky , C Bailey
Published: May 2021

Objective

This prospective controlled observational cohort pilot study investigated a potential blood-based biomarker [α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] and relationship to neurocognitive testing in collegiate athletes.

Methods

A multisport sample of 60 collegiate athletes (53% female; 44 contact, 16 non-contact controls) completed ImPACT testing and provided blood samples at a pre-season baseline and within 4 weeks post-season. Plasma and serum samples were processed for AMPAR peptides and antibodies. Twelve athletes did not complete all procedures and were excluded from the final analysis (final n = 48; 36 contact; 12 controls).

Results

Contact athletes demonstrated greater increases in serum AMPAR antibodies compared to controls (t(46) = 3.24;p < 0.01). On neurocognitive testing, controls had a faster reaction time than contact athletes at baseline (p < 0.05); however, this increased post season (p < 0.01), with the mean change in reaction time (contact: M = 0.06, SD = 0.19; control: M = 0.00, SD = 0.04) approaching significance (t(37.23) = 1.54; p < 0.15). Additionally, ImPACT reaction time was correlated (r = 0.37;p < 0.05) with serum AMPAR antibodies, with slowed reaction time related to increased AMPAR in contact athletes only and only post-season.

Conclusions

Serum AMPAR antibody levels significantly increased in the contact group and were correlated with reaction time on contact athlete neurocognitive testing at post-season only, with contact athletes showing both slower reaction time and increased levels of AMPAR antibodies compared to controls. No findings were identified in plasma AMPAR peptides, possibly related to sample processing which could not be done immediately in this pilot study. Future research and replication is needed; however, AMPAR may represent a blood-based concussion biomarker, with potential for clinical utility in athletes.
A - 29 Language Differences in Neurocognitive Scores and Symptom Report in Professional Football Players
Authors: R Wagner , P Arends , M Varkovetski , D Naidu , M Mrazik
Published: May 2021

Objective

The purpose of this study was to investigate the role of language on neurocognitive test outcomes and concussion symptom ratings in professional football players.

Methods

Design/Setting - A retrospective cross-section analysis of 1546 male Canadian Football League (CFL) athletes was conducted using baseline data collected from the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) across the 2016–18 competitive seasons. Independent Variables - Participants (1546) were divided into three language categories, native English-speaking, bilingual – whose first language was English, and English as a second language (ESL). Years of education, age, and concussion history were entered as co-variates. Outcome Measure -The 5 Composite scores from ImPACT and the 22 symptoms from the post-concussion symptom scale (PCSS).

Results

Results of the MANCOVA showed no significant differences between language groups on any of the five ImPACT composite scores F(10, 3072) = 1.09, p = 0.36. The Kruskall-Wallis test revealed significant differences were found in three symptoms including dizziness [X2(2, 1486) = 32.85, p < 0.001)], sadness [X2(2, 1486) = 6.505, p = 0.04], and concentration [X2(2, 1486) = 11.01, p = 0.004)] with the bilingual and non-native English speakers having higher scores.

Conclusions

This study suggests that cultural and linguistic differences should be considered when administering CNTs. While differences in cognitive outcomes have not been consistently found across studies, differences in baseline symptom reports have been consistently demonstrated. Information pertaining to a patient’s level of acculturation and language proficiency is important for examiners when working with diverse populations. Continuing to develop language-specific normative databases is encouraged.
The Effects of Adult Aging and Culture on Theory of Mind
Authors: Yong Min Hooi , Lawrie Louisa , Schaefer Alexandre , Phillips Louise H
Published: May 2021

Objectives

Older adults tend to have poorer Theory of Mind (ToM) than their younger counterparts, and this has been shown in both Western and Asian cultures. We examined the role of working memory (WM) in age differences in ToM, and whether this was moderated by education and culture (the United Kingdom vs. Malaysia).

Methods

We used 2 ToM tests with differing demands on updating multiple mental states (false belief) and applying social rules to mental state processing (faux pas). We also looked at the role of education, socioeconomic status, and WM. A total of 298 participants from the United Kingdom and Malaysia completed faux pas, false belief, and WM tasks.

Results

Age effects on some aspects of ToM were greater in the Malaysian compared to the UK sample. Malaysian older adults were poorer at faux pas detection, aspects of false belief, and WM compared to young adults. In subsequent moderated mediation analyses, we found that, specifically in the Malaysian sample, the mediating effects of WM on the age and ToM relationship occurred at the lowest levels of education.

Discussion

This pattern of results may reflect changes in the familiarity and cognitive load of explicit mental state attribution, along with cultural differences in the pace and nature of cognitive aging. Cultural differences in education and WM should be considered when researching age differences in ToM.
Two high-quality de novo genomes from single ethanol-preserved specimens of tiny metazoans (Collembola)
Authors: Schneider Clément , Woehle Christian , Greve Carola , D'Haese Cyrille A , Wolf Magnus , Hiller Michael , Janke Axel , Bálint Miklós , Huettel Bruno
Published: May 2021

Background

Genome sequencing of all known eukaryotes on Earth promises unprecedented advances in biological sciences and in biodiversity-related applied fields such as environmental management and natural product research. Advances in long-read DNA sequencing make it feasible to generate high-quality genomes for many non–genetic model species. However, long-read sequencing today relies on sizable quantities of high-quality, high molecular weight DNA, which is mostly obtained from fresh tissues. This is a challenge for biodiversity genomics of most metazoan species, which are tiny and need to be preserved immediately after collection. Here we present de novo genomes of 2 species of submillimeter Collembola. For each, we prepared the sequencing library from high molecular weight DNA extracted from a single specimen and using a novel ultra-low input protocol from Pacific Biosciences. This protocol requires a DNA input of only 5 ng, permitted by a whole-genome amplification step.

Results

The 2 assembled genomes have N50 values >5.5 and 8.5 Mb, respectively, and both contain ∼96% of BUSCO genes. Thus, they are highly contiguous and complete. The genomes are supported by an integrative taxonomy approach including placement in a genome-based phylogeny of Collembola and designation of a neotype for 1 of the species. Higher heterozygosity values are recorded in the more mobile species. Both species are devoid of the biosynthetic pathway for β-lactam antibiotics known in several Collembola, confirming the tight correlation of antibiotic synthesis with the species way of life.

Conclusions

It is now possible to generate high-quality genomes from single specimens of minute, field-preserved metazoans, exceeding the minimum contig N50 (1 Mb) required by the Earth BioGenome Project.
MesKit: a tool kit for dissecting cancer evolution of multi-region tumor biopsies through somatic alterations
Authors: Liu Mengni , Chen Jianyu , Wang Xin , Wang Chengwei , Zhang Xiaolong , Xie Yubin , Zuo Zhixiang , Ren Jian , Zhao Qi
Published: May 2021

Background

Multi-region sequencing (MRS) has been widely used to analyze intra-tumor heterogeneity (ITH) and cancer evolution. However, comprehensive analysis of mutational data from MRS is still challenging, necessitating complicated integration of a plethora of computational and statistical approaches.

Findings

Here, we present MesKit, an R/Bioconductor package that can assist in characterizing genetic ITH and tracing the evolutionary history of tumors based on somatic alterations detected by MRS. MesKit provides a wide range of analysis and visualization modules, including ITH evaluation, metastatic route inference, and mutational signature identification. In addition, MesKit implements an auto-layout algorithm to generate phylogenetic trees based on somatic mutations. The application of MesKit for 2 reported MRS datasets of hepatocellular carcinoma and colorectal cancer identified known heterogeneous features and evolutionary patterns, together with potential driver events during cancer evolution.

Conclusions

In summary, MesKit is useful for interpreting ITH and tracing evolutionary trajectory based on MRS data. MesKit is implemented in R and available at https://bioconductor.org/packages/MesKit under the GPL v3 license.
Direct Caregiving in Older Adults: How Systems of Care Perpetuate the Grand Challenges and What Social Workers Can Do about It
Authors: Kusmaul Nancy , Wladkowski Stephanie P
Published: May 2021

Direct care workers (DCWs) provide personal care, emotional support, and companionship, helping older adults maintain quality lives. DCWs earn low wages, have little training, and experience high turnover rates. While the demand for DCWs grows, real wages continue to fall. Undervaluing DCWs threatens the continuity and quality of care that older adults receive. Through the social work grand challenges lens, this article discusses two qualitative studies, in home care (n = 24) and nursing homes (n = 23), that demonstrate that while DCWs help advance long and productive lives, they experience extreme economic inequality and lack equal opportunity and justice. The article concludes with a discussion of social work’s role in advancing opportunity and justice.
Evolution and application of digital technologies to predict crop type and crop phenology in agriculture
Authors: Potgieter Andries B , Zhao Yan , Zarco-Tejada Pablo J , Chenu Karine , Zhang Yifan , Porker Kenton , Biddulph Ben , Dang Yash P , Neale Tim , Roosta Fred , Chapman Scott
Published: May 2021

The downside risk of crop production affects the entire supply chain of the agricultural industry nationally and globally. This also has a profound impact on food security, and thus livelihoods, in many parts of the world. The advent of high temporal, spatial and spectral resolution remote sensing platforms, specifically during the last 5 years, and the advancement in software pipelines and cloud computing have resulted in the collating, analysing and application of ‘BIG DATA’ systems, especially in agriculture. Furthermore, the application of traditional and novel computational and machine learning approaches is assisting in resolving complex interactions, to reveal components of ecophysiological systems that were previously deemed either ‘too difficult’ to solve or ‘unseen’. In this review, digital technologies encompass mathematical, computational, proximal and remote sensing technologies. Here, we review the current state of digital technologies and their application in broad-acre cropping systems globally and in Australia. More specifically, we discuss the advances in (i) remote sensing platforms, (ii) machine learning approaches to discriminate between crops and (iii) the prediction of crop phenological stages from both sensing and crop simulation systems for major Australian winter crops. An integrated solution is proposed to allow accurate development, validation and scalability of predictive tools for crop phenology mapping at within-field scales, across extensive cropping areas.
Rising to the challenges of the pandemic: Telehealth innovations in U.S. emergency departments
Authors: Uscher-Pines Lori , Sousa Jessica , Mehrotra Ateev , Schwamm Lee H , Zachrison Kori S
Published: May 2021

Objective

During the first 9 months of the coronavirus disease 2019 (COVID-19) pandemic, many emergency departments (EDs) experimented with telehealth applications to reduce virus exposure, decrease visit volume, and conserve personal protective equipment. We interviewed ED leaders who implemented telehealth programs to inform responses to the ongoing COVID-19 pandemic and future emergencies.

Materials and Methods

From September to November 2020, we conducted semi-structured interviews with ED leaders across the United States. We identified EDs with pandemic-related telehealth programs through literature review and snowball sampling. Maximum variation sampling was used to capture a range of experiences. We used standard qualitative analysis techniques, consisting of both inductive and deductive approaches to identify and characterize themes.

Results

We completed 15 interviews with EDs leaders in 10 states. From March to November 2020, participants experimented with more than a dozen different types of telehealth applications including tele-isolation, tele-triage, tele-consultation, virtual postdischarge assessment, acute care in the home, and tele-palliative care. Prior experience with telehealth was key for implementation of new applications. Most new telehealth applications turned out to be temporary because they were no longer needed to support the response. The leading barriers to telehealth implementation during the pandemic included technology challenges and the need for “hands-on” implementation support in the ED.

Conclusions

In response to the COVID-19 pandemic, EDs rapidly implemented many telehealth innovations. Their experiences can inform future responses.
Intratumoral Intensity in T2-weighted MRI and the Association With Histological and Molecular Prognostic Factors in Women With Invasive Breast Cancer
Authors: de Paula Ivie Braga , Pena Gil Patrus , Barbosa Andre Luis , Oliveira Guilherme Jose de Paula , Ferreira Samuel Silva , Cordeiro Leonardo Passos Vilares
Published: May 2021

Objective

To compare the intratumoral T2 signal intensity on MRI and histopathological and molecular expression of biomarkers of aggressiveness (histological grade, hormonal status, HER2, and Ki-67).

Methods

This retrospective study included all women with invasive breast cancer undergoing MRI from January 2014 to October 2016. The intratumoral T2 signal as interpreted at consensus by two radiologists was compared to histopathological and molecular prognostic factors from the surgical specimen. Statistical analyses used Pearson χ 2 test with a confidence level of 95% (P ≤ 0.05).

Results

Fifty patients with 50 lesions met study criteria (mean age 65.8 ± 13.5 years). Mean lesion size was 28 mm ± 15.7 mm (range, 15 to 76 mm). Cancer types were invasive ductal (35/50, 70%), invasive lobular (10/50, 20%), and mixed (5/50, 10%). Most lesions were histological grade 1 or 2 (41/50, 82%) and luminal type (45/50, 90%). On T2 images, lesions were hypointense in 62% (31/50), isointense in 20% (10/50), and hyperintense in 18% (9/50) of cases. Among hypointense lesions, 94% (29/31) were low or intermediate grade tumors (P = 0.02), low HER2 overexpression (30/31, 97%) (P = 0.005), and high ER status (30/31, 97%) (P = 0.006), high PR (26/31, 84%) (P = 0.02), and low incidence of necrosis (2/31, 6%). The difference in Ki-67 tumoral expression between groups was not significant.

Conclusion

Intratumoral T2 hypointensity in invasive breast cancer is associated with better prognostic tumors, such as histological low-grade high hormone receptor status.
Feasibility of conversion thoracoscopic esophagectomy after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma
Authors: Kubo Kentaro , Kanematsu Kyohei , Kurita Daisuke , Ishiyama Koshiro , Oguma Junya , Itami Jun , Daiko Hiroyuki
Published: May 2021

Background

Recently, patients with cT4b esophageal cancer often require conversion surgery following induction therapy, for which the standard procedure is open esophagectomy. However, thoracoscopic esophagectomy, including thoracoscopic esophagectomy in the prone position, is increasingly used. We compared short-term outcomes of thoracoscopic esophagectomy and open esophagectomy in this setting.

Methods

We retrospectively analyzed 14 patients who underwent thoracoscopic esophagectomy, and 10 who underwent open esophagectomy, for locally advanced unresectable esophageal cancer after induction therapy between March 2007 and July 2020.

Results

The two groups did not significantly differ in patient background. Median total and thoracic surgical times were both significantly longer for open esophagectomy than for thoracoscopic esophagectomy. Median blood loss was also greater in the open esophagectomy group than in the thoracoscopic esophagectomy group. The thoracoscopic esophagectomy group also had significantly shorter median chest drain duration; and lower C-reactive protein levels on the second and third postoperative days. The two groups did not significantly differ in total complications or postoperative hospital stay.

Conclusions

Thoracoscopic esophagectomy is as safe and feasible as open esophagectomy for conversion surgery after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.
Opioids, Double Effect, and the Prospects of Hastening Death
Authors: Reed Philip A
Published: May 2021

The relevance of double effect for end-of-life decision-making has been challenged recently by a number of scholars. The principal reason is that opioids such as morphine do not usually hasten death when administered to relieve pain at the end of life; therefore, no secondary “double” effect is brought about. In my article, I argue against this view, showing how the doctrine of double effect is relevant to the administration of opioids at the end of life. I contend that the prevailing view suffers from a misunderstanding of the nature of double effect, which includes application to risking a grave harm.
Principles, Paradigms, and Protections
Authors: Hawking Michael K
Published: May 2021

The breadth of themes addressed in this issue of the Journal of Medicine and Philosophy is striking. These articles brim with some of the most foundational questions one can ask in bioethics and the philosophy of medicine: Under what circumstances might we risk some harm in pursuit of a greater good? In the setting of experimental therapies, how should we weigh the potential risk and benefit for an individual patient against the broader potential benefit realized for society as a whole? How might we consistently differentiate health from pathology? Under what circumstances might we say that a human being has died? Does acknowledging particular things (such as play) as good generate duties? Duties for whom and enforced by whom? These articles share a preoccupation with foundational questions that must be addressed in any sound bioethics curriculum, and they make clear that our answers to these questions are not simply theoretical but manifest in policy and in practice.