bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency, Timing, and Prediction of Major Bleeding Complications From Percutaneous Renal Biopsy
Authors: Schorr Melissa , Roshanov Pavel S. , Weir Matthew A. , House Andrew A.
Published: May 2020

Background and Objectives:

The risk and timing of bleeding events following ultrasound-guided percutaneous renal biopsy are not clearly defined.

Design setting, participants, and measurements:

We performed a retrospective study of 617 consecutive adult patients who underwent kidney biopsy between 2012 and 2017 at a tertiary academic hospital in London, Canada. We assessed frequency and timing of minor (not requiring intervention) and major (requiring blood transfusion, surgery, or embolization) bleeds and developed a personalized risk calculator for these.

Results:

Bleeding occurred in 79 patients (12.8%; 95% confidence interval [CI]: 10.4%-15.7%). Minor bleeding occurred in 67 patients (10.9%; 95% CI: 8.6%-13.6%). Major bleeding occurred in 12 patients (1.9%; 95% CI: 1.1%-3.4%); 2 required embolization or surgery (0.3%; 95% CI: 0.09%-1.2%) and 10 required blood transfusion (1.6%; 95% CI: 0.9%-3.0%). Seventy-three of 79 events were identified immediately on post-procedure ultrasound (92.4% of cases; 95% CI: 84.4%-96.5%). Four of 617 patients experienced a minor event not detected immediately (0.6%; 95% CI: 0.3%-1.7%). Two patients (0.3%; 95% CI: 0.09%-1.2%) suffered a major complication that was not recognized immediately; both required blood transfusions only. There were no deaths or nephrectomies. A risk calculator using age, body mass index, platelet count, hemoglobin concentration, size of the target kidney, and whether the kidney is native, or an allograft predicted minor (C-statistic, 0.70) and major bleeding (C-statistic, 0.83).

Conclusions:

This retrospective study of 617 patients who had percutaneous ultrasound-guided renal biopsies supports the safety of short post-biopsy monitoring for most patients. A risk calculator can further personalize estimates of complication risk ( http://perioperativerisk.com/kbrc ).
Employing Technology Industry Methods to Facilitate Transformative Learning Experiences in the Classroom: Insights From a Pilot
Authors: Shonkoff Eleanor T. , Fitopoulos Theodore , Folta Sara C.
Published: May 2020

High-impact, transformative educational practices change the way students see themselves and others, as well as impart knowledge. Practices from the technology industry may offer innovative strategies for fostering transformational learning experiences. We developed and implemented two innovation techniques—Hackathon and Innovation Time Off (ITO)—in a graduate course on social psychology and public health nutrition. The Hackathon occurred in the sixth and seventh weeks of the course; the last 4 weeks provided 10% of class time for ITO projects. All enrolled students participated in the pilot study ( n = 6; M age = 27.5 years; 83% female; 67% White) and completed reflection papers during the final exam period. Student learning was assessed from these reflection papers using a rubric for transformative versus nontransformative changes in five areas: confidence, pride, skills, perspective, and identity. Student responses revealed transformative changes in perspective ( n = 7). Additionally, nontransformative changes were found in confidence ( n = 1), identity ( n = 2), perspective ( n = 4), and skills ( n = 9). This pilot work suggests that the Hackathon and ITO contributed to perceived skill-building in problem-solving and teamwork, and the Hackathon may have led to transformative changes in perspective; ITO may not be appropriate for learners who need structure; high confidence remained unchanged; and these strategies are likely to be feasible and replicable.
Atomic-Resolution EDX, HAADF, and EELS Study of GaAs1-xBix Alloys
Authors: Paulauskas Tadas , Pačebutas Vaidas , Butkutė Renata , Čechavičius Bronislovas , Naujokaitis Arnas , Kamarauskas Mindaugas , Skapas Martynas , Devenson Jan , Čaplovičová Mária , Vretenár Viliam , Li Xiaoyan , Kociak Mathieu , Krotkus Arūnas
Published: May 2020

The distribution of alloyed atoms in semiconductors often deviates from a random distribution which can have significant effects on the properties of the materials. In this study, scanning transmission electron microscopy techniques are employed to analyze the distribution of Bi in several distinctly MBE grown GaAs1−xBix alloys. Statistical quantification of atomic-resolution HAADF images, as well as numerical simulations, are employed to interpret the contrast from Bi-containing columns at atomically abrupt (001) GaAs-GaAsBi interface and the onset of CuPt-type ordering. Using monochromated EELS mapping, bulk plasmon energy red-shifts are examined in a sample exhibiting phase-separated domains. This suggests a simple method to investigate local GaAsBi unit-cell volume expansions and to complement standard X-ray-based lattice-strain measurements. Also, a single-variant CuPt-ordered GaAsBi sample grown on an offcut substrate is characterized with atomic scale compositional EDX mappings, and the order parameter is estimated. Finally, a GaAsBi alloy with a vertical Bi composition modulation is synthesized using a low substrate rotation rate. Atomically, resolved EDX and HAADF imaging shows that the usual CuPt-type ordering is further modulated along the [001] growth axis with a period of three lattice constants. These distinct GaAsBi samples exemplify the variety of Bi distributions that can be achieved in this alloy, shedding light on the incorporation mechanisms of Bi atoms and ways to further develop Bi-containing III-V semiconductors.
Vestibular migraine with Wallenberg syndrome: a case report
Authors: Xin Ying , Fu Junyi , Xie Longchang , Yang Jie , Ke Guanhao
Published: May 2020

Background

Vestibular migraine, a kind of acute vestibular syndrome, leads to both migraines and vertigo symptoms in a single patient. The occurrence of vestibular migraine has shown an obvious increase in female groups based on age. Though it is recognized that migraines may cause ischemic lesions in some brain regions, the relationship between vestibular migraine and cerebral infarction has seldom been reported, especially with no known research reports about vestibular migraine with Wallenberg syndrome. Based on this, the connection of the two diseases needs to be the focus of more research.

Case presentation

The patient, a 35-year-old lady, came to our department with severe vertigo and headaches for approximately two years. She suffered from migraines which attacked about twice yearly for nearly a decade. The diffusive weighted imaging showed a subacute infarction in the right lateral medullar. The clinical characteristics and MRI findings supported the diagnosis of vestibular migraine with Wallenberg syndrome. Along with the normal routine medication for vestibular migraine with Wallenberg syndrome, we also prescribed migraine therapy at the same time. In a 3-month follow-up, the patient had suffered only one vertigo attack and she reported that the migraines were less common and less intense than she was previously experiencing.

Conclusions

Due to the fact that vestibular migraine is one of the risk factors of cerebral ischemia, we need to pay more attention to this phenomenon. The current case suggests that both routine medication on ischemic stroke as well as treatment for migraines should be used concurrently in vestibular migraine with Wallenberg syndrome.
Open tibia plateau fracture with intra-osseous dislocation of the patella and quadriceps tendon rupture: a case report
Authors: Zhao Daohong , Li Weiqiang , Liu Luping , Lu Ning , Chen Leijie , Zhang Jun
Published: May 2020

Background

Both tibial plateau fractures and extensor apparatus injuries are serious injuries to the knee joint that generally do not occur in the same patient. We report a rare case of open tibial plateau fracture combined with quadriceps tendon rupture and complete displacement of the patella into the tibial plateau fracture.

Case presentation

The case involved a male who was 19 years old who had been in a motorcycle accident. The patient was admitted to our department with an open tibial plateau fracture 3 h post-injury. X-ray showed a tibial plateau fracture and complete displacement of the patella into the tibial plateau. CT showed an avulsion fracture in the patella and tibial intercondylar eminence. Concomitant quadriceps tendon injury and both anterior and posterior cruciate ligament tibial insertion avulsion fractures were considered. The operative findings of emergency surgery confirmed our preoperative diagnosis. Single-stage quadriceps tendon repair and ORIF for the tibial plateau fracture were performed. Satisfactory restoration of function was acquired at the last follow up.

Conclusion

The most difficult aspect of this case was the determination of the cause of the intra-osseous dislocation of the patella into the tibial plateau. The most likely mechanism of the injury may be that the patient experienced transient posterior dislocation of the knee during the injury. Rupture of the quadriceps tendon should be considered with posterior dislocation of the knee, and the patella was pushed into the tibial plateau fracture by force after the rupture of the quadriceps tendon.
Exam performance of different admission quotas in the first part of the state examination in medicine: a cross-sectional study
Authors: Mommert Alex , Wagner Josefin , Jünger Jana , Westermann Jürgen
Published: May 2020

Background

Most medical students in Germany are admitted via selection procedures, which are adjusted to the demands of the universities. At Lübeck medical school, scores from interviews that measure non-academic skills and pre-university GPAs are summed to arrive at an admission decision. This article seeks to illuminate the effectiveness of this selection procedure in comparison to other non-selected student groups.

Methods

Quota information and exam results from the first federal exam were linked for students admitted to Lübeck medical school between 2012 and 2015 (N = 655). Five different student groups (university-specific selection quota, pre-university GPA quota, waiting time quota, ex-ante quota and foreign students) were compared regarding exam attempts, written and oral grades, temporal continuity and examination success in the standard study period.

Results

While the pre-university GPA quota outperformed all other quotas regarding written and oral grades, it did not differ from the selection quota regarding exam attempts, temporal continuity and examination success in the standard study period. Students in the waiting time and ex-ante quotas performed inferior by comparison. The results of foreign students were the most problematic.

Conclusion

Students selected by the university show high temporal continuity and examination success. These results, and possible advantages in physician eligibility, argue for the utilisation of non-academic skills for admission.
Delayed diagnosis of fatal pneumonic canine plague: clinical and pathologic features in two naturally infected Colorado dogs
Authors: Schaffer Paula A. , Hershkowitz Connor S. , Dowers Kristy L. , Golchanour Jennifer L. , Harris Lauren J. , Aboellial Tawfik A. , Morley Paul S. , Brault Stephanie A. , Pabilonia Kristy L. , Mason Gary L. , House Jennifer A. , Daniels Joshua B.
Published: May 2020

Background

Plague caused byYersinia pestisis a highly infectious and potentially fatal zoonotic disease that can be spread by wild and domestic animals. In endemic areas of the northern hemisphere plague typically cycles from March to October, when flea vectors are active. Clinical forms of disease include bubonic, septicemic, and pneumonic plague. All clinical forms are uncommon in dogs and the pneumonic form is exceedingly rare.

Case presentation

Two mixed breed young-adult male domestic dogs presented to Colorado veterinarians with fever and vague signs that progressed to hemoptysis within 24 h. Case 1 presented in June 2014, while Case 2 occurred in December 2017. Thoracic radiography of Case 1 and 2 revealed right dorsal and right accessory lobe consolidation, respectively. In Case 1 initial differential diagnoses included pulmonary contusion due to trauma or diphacinone toxicosis. Case 1 was euthanized ~ 24 h post presentation due to progressive dyspnea and hemoptysis. Plague was confirmed 9 days later, after the dog’s owner was hospitalized with pneumonia. Case 2 was treated as foreign body/aspiration pneumonia and underwent lung lobectomy at a veterinary teaching hospital. Case 2 was euthanized after 5 days of hospitalization when bacterial culture of the excised lobe yieldedYersinia pestis. Both dogs had severe diffuse necrohemorrhagic and suppurative pneumonia at post mortem examination.

Conclusions

Both dogs were misdiagnosed due to the atypical lobar presentation of an extremely rare form of plague in a species that infrequently succumbs to clinical disease. Presentation outside of the typical transmission period of plague was also a factor leading to delayed diagnosis in Case 2. Erroneous identification by automated bacterial identification systems was problematic in both cases. In endemic areas, plague should be ruled out early in febrile dogs with acute respiratory signs, hemoptysis, lobar or diffuse pathology, and potential for exposure, regardless of season. Seasonal and geographic distributions of plague may shift with climate change, so vigilance by primary care veterinarians is warranted. Timely submission of samples to a veterinary diagnostic laboratory could expedite accurate diagnosis and reduce potential for human and domestic animal exposure.
Results from a 2018 cross-sectional survey in Tokyo, Osaka and Sendai to assess tobacco and nicotine product usage after the introduction of heated tobacco products (HTPs) in Japan
Authors: Adamson Jason , Kanitscheider Claudia , Prasad Krishna , Camacho Oscar M. , Beyerlein Elisabeth , Bhagavan Yoga Keralapura , Proctor Christopher , Murphy James
Published: May 2020

Background

For novel tobacco products that potentially reduce the risk of tobacco harm, post-market surveillance is important to observe population usage and behaviours associated with everyday use. This pilot study was performed to examine the use of tobacco products in three Japanese urban regions.

Methods

This study was a cross-sectional epidemiological survey administered in Sendai, Tokyo and Osaka, Japan, from May 19th to June 25th, 2018. Participants were selected with a three-stage probability random sampling process that first identified primary sampling units, then households and finally individuals. Eligible participants were aged at least 20 years who were willing to participate after information about the study was provided. People younger than 20 years and those living in institutions were excluded. Questionnaires were paper based and administered door to door.

Results

Responses were obtained from 4154 participants. Sixty-five percent self-reported being never, 19% current and 16% former users of any tobacco product at the time of the survey. Combustible tobacco products (almost all being cigarette) were used most (16%) followed by HTPs (5%). In the categories of combustible tobacco users and HTP users, 70% and 16%, respectively, used these products exclusively. Dual use was reported by 11% of respondents. Compared with 12 months before the survey, 12% of sole combustible tobacco products users were using HTPs exclusively or as dual users and 6% had quit tobacco products completely; 94% of sole HTP users remained sole users and 4% had quit tobacco products completely; and amongst dual users 12% had reverted to exclusive use of combustible tobacco products, 14% had switched to sole use of HTPs and 4% had quit tobacco products completely.

Conclusion

HTPs seem to be accepted as an alternative tobacco product amongst combustible tobacco users. Given complex findings for dual use, improved understanding of the motivations underlying this behaviour would be of interest.
Development of two psychological experience questionnaires for screening violence-related mental health disorders of non-psychiatric inpatients
Authors: Meng Yanjun , Li Yuling , Cao Hongbao , Xu Yong , Wang Binquan
Published: May 2020

Background

Increased violent events happen in the general hospitals in China and yet non-psychiatric departments do not have tools for violence-tendency screening.

Methods

The current study developed and evaluated two Inpatient Psychological Experience Questionnaires (IPEQs) for the screening of violence-related six mental health disorders: (Inpatient Psychological Experience Questionnaire-1 (IPEQ-1): anxiety, depression and suicidality; Inpatient Psychological Experience Questionnaire-2 (IPEQ-2): paranoid personality disorder, emotionally unstable personality disorder and histrionic personality disorder). Two initial IPEQs (IPEQ-1: 37 items and IPEQ-2: 30 items) were developed and assessed by domain experts. Then 1210 inpatients were recruited and divided into three groups (160, 450 and 600 samples, respectively) for IPEQs item selection and evaluation. During the two-stage item selection, three statistical methods including Pearson’s correlation coefficient, exploratory factor analysis and item response theory were applied. For the item evaluation, Cronbach’s alpha coefficient, test-retest reliability, criterion-related validity and construct validity of the final questionnaires were measured.

Results

Twelve items were selected for each IPEQs. Cronbach’s alpha coefficients were 0.91 and 0.78 for IPEQ-1 and IPEQ-2, respectively. Test-retest replication ratios were 0.95 and 0.87 for IPEQ-1 and IPEQ-2, respectively. Correlation coefficients between different disorders and their related-tools scores were [0.51, 0.44] and [0.40, 0.44] for IPEQ-1 and IPEQ-2, respectively and were significant (P < 0.01). Confirmatory factor analysis supported the validity of the final IPEQs (P < 0.05), and the model fit index met the criterion generally.

Conclusion

The IPEQs developed in this study could be effective and easy-to-use tools for screening inpatients with violence-intendancy in non-psychosomatic departments.
Initial experience of complete laparoscopic radical nephroureterectomy combined with transvesical laparoscopic excision of distal ureter in patients with upper urinary tract cancer
Authors: Miyake Makito , Nishimura Nobutaka , Aoki Katsuya , Ohmori Chihiro , Shimizu Takuto , Owari Takuya , Hori Shunta , Morizawa Yosuke , Gotoh Daisuke , Nakai Yasushi , Anai Satoshi , Torimoto Kazumasa , Tanaka Nobumichi , Fujimoto Kiyohide
Published: May 2020

Background

Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC).

Methods

A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation.

Results

The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31).

Conclusions

We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value.
Sarcomatoid carcinoma of the pancreas with rare long-term survival: a case report
Authors: Kimura Toshihisa , Fujimoto Daisuke , Togawa Tamotsu , Ishida Makoto , Iida Atsushi , Sato Yasunori , Goi Takanori
Published: May 2020

Background

Sarcomatoid carcinoma of the pancreas (SCP) tends to have similar or even worse prognosis than that of conventional pancreatic ductal adenocarcinoma. The clinical and pathological features of SCP remain poorly characterized owing to its rarity.

Case presentation

A 58-year-old man was admitted to our hospital with the chief complaints of upper abdominal pain and weight loss. Abdominal contrast computed tomography revealed a 5-cm low-density mass in the pancreatic body. Magnetic resonance cholangiopancreatography revealed an obstruction of the main pancreatic duct and a dilation of the distal main pancreatic duct. Based on the clinicoradiological findings, pancreatic body cancer was suspected, and the distal pancreatectomy was performed. A pathological examination revealed that the tumor was composed of an area of invasive ductal adenocarcinoma and an area of sarcomatous spindle-shaped cells; the latter component predominated. The spindle cells were immunohistochemically positive for both cytokeratin and vimentin, and thus, a pathological diagnosis of SCP was made. In addition, immunohistochemical analysis suggested the sarcomatous component might be derived from the adenocarcinoma component via the process of epithelial-mesenchymal transition. After the operation, the patient received 6 months of chemotherapy with gemcitabine. At 10 years after the operation, the patient is alive with no recurrence.

Conclusions

The current case study presented a SCP patient with long-term survival after the operation. It was worth noting that the sarcomatous component of the tumor pathologically showed lower MIB-1 labeling index compared with those in previously reported SCP cases, which might account for the long-term survival of the patient.
Circadian changes in the composition of human milk macronutrients depending on pregnancy duration: a cross-sectional study
Authors: Paulaviciene Ieva Jura , Liubsys Arunas , Molyte Alma , Eidukaite Audrone , Usonis Vytautas
Published: May 2020

Background

The purpose of this study was to evaluate the circadian variation of human milk macronutrients and energy content depending upon pregnancy duration.

Methods

One hundred eighty fresh human milk samples from 45 mothers (27 of preterm and 18 of full-term newborns) were collected on a single day chosen between the 14th to 16th day after delivery. The samples were taken four times per day at 12 PM, 6 PM, 12 AM and 6 AM. Only lactating women, who could not breastfeed their hospitalized newborns and expressed milk by breast pump, were enrolled in the study. Human milk macronutrient composition and energy count were evaluated by mid-infrared spectrophotometry.

Results

Significant differences in macronutrient content were observed between 6 AM and 12 PM for mean protein content (t = − 4.62, df = 44, p < 0.001), for mean fat content (t = − 2.10, df = 44, p = 0.04) and for mean energy content (t = − 2.24, df = 44, p = 0.03); between 6 AM and 6 PM for mean protein content (t = − 2.41, df = 43, p = 0.02), for mean fat content (t = − 3.76, df = 43, p = 0.001) and for mean energy content (t = − 3.85, df = 43, p < 0.001); between 12 PM and 12 AM for mean protein content (Wilcoxon test V = 75.5, p = 0.001), for mean fat content (t = 2.50, df = 44, p = 0.02) and for mean energy content (t = 2.74, df = 44, p = 0.01); between 6 PM and 12 AM for mean protein content (V = 229, p = 0.02), for mean fat content (t = 4.39, df = 43, p < 0.001) and for mean energy content (t = − 4.57, df = 43, p < 0.001). The average content of carbohydrates did not change significantly during the 24 h. The samples of preterm newborns’ mothers had more apparent diurnal fluctuations in macronutrient content.

Conclusions

Our study revealed significant diurnal variations in protein and fat in human milk, and these circadian fluctuations were more apparent in the milk of mothers of preterm infants.
Precise parallel volumetric comparison of molecular surfaces and electrostatic isopotentials
Authors: Georgiev Georgi D. , Dodd Kevin F. , Chen Brian Y.
Published: May 2020

Geometric comparisons of binding sites and their electrostatic properties can identify subtle variations that select different binding partners and subtle similarities that accommodate similar partners. Because subtle features are central for explaining how proteins achieve specificity, algorithmic efficiency and geometric precision are central to algorithmic design. To address these concerns, this paper presents pClay, the first algorithm to perform parallel and arbitrarily precise comparisons of molecular surfaces and electrostatic isopotentials as geometric solids. pClay was presented at the 2019 Workshop on Algorithms in Bioinformatics (WABI 2019) and is described in expanded detail here, especially with regard to the comparison of electrostatic isopotentials. Earlier methods have generally used parallelism to enhance computational throughput, pClay is the first algorithm to use parallelism to make arbitrarily high precision comparisons practical. It is also the first method to demonstrate that high precision comparisons of geometric solids can yield more precise structural inferences than algorithms that use existing standards of precision. One advantage of added precision is that statistical models can be trained with more accurate data. Using structural data from an existing method, a model of steric variations between binding cavities can overlook 53% of authentic steric influences on specificity, whereas a model trained with data from pClay overlooks none. Our results also demonstrate the parallel performance of pClay on both workstation CPUs and a 61-core Xeon Phi. While slower on one core, additional processor cores rapidly outpaced single core performance and existing methods. Based on these results, it is clear that pClay has applications in the automatic explanation of binding mechanisms and in the rational design of protein binding preferences.
Saccadic reaction time and ocular findings in phenylketonuria
Authors: Hopf Susanne , Nowak Caroline , Hennermann Julia B. , Schmidtmann Irene , Pfeiffer Norbert , Pitz Susanne
Published: May 2020

Background

Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. Despite some obvious ocular changes, the disorder has been poorly recognized by ophthalmologists. Neurophysiologic tests imply prolonged reaction time correlating with increased phenylalanine blood concentrations. We aimed to test saccadic reaction time in PKU patients in dependency of blood phenylalanine concentrations.

Methods

Nineteen biochemically diagnosed PKU patients and 100 controls completed comprehensive ophthalmologic and orthoptic examinations including saccadometry by infrared based video-oculography. Peak velocity, gain, and particularly latency of reflexive saccades were compared to controls, and regression analysis was performed.

Results

Latency of reflexive saccades was not associated with the current phenylalanine concentration. Although in 10 out of 19 patients phenylalanine concentrations were outside the age-related therapeutic range, latency differed little between PKU patients and the controls, as well as peak velocity and gain. Ocular findings occurred as partial hypopigmentation of the iris in one late diagnosed patient aged 36 years, and as bilateral cataracts (possibly due to steroid intake) with refractive amblyopia, strabismus, high myopia, and glaucoma in another late diagnosed patient aged 46 years. Visual acuity was reduced in eight PKU patients.

Conclusions

Saccadometry, particularly saccadic reaction time, is not useful in the monitoring of phenylketonuria. Ophthalmic examination is recommended in PKU patients, as the occurrence of ocular pathologies was relatively high.
Potential influence of parental copy number variations on noninvasive prenatal testing (NIPT): two case reports
Authors: Qi Yiming , Yang Jiexia , Hou Yaping , Hu Rong , Wang Dongmei , Peng Haishan , Yin Aihua
Published: May 2020

Background

Small subchromosomal deletions and duplications caused by copy number variants (CNVs) can now be detected with noninvasive prenatal testing (NIPT) technology. However, the clinical utility and validity of this screening for CNVs are still unknown. Here, we discuss some special conditions in which both cases simultaneously exhibited false positives caused by maternal CNVs and false negatives due to limitations of the technology.

Case presentation

In case 1, NIPT indicated a 1.1 Mb deletion at 21q21.1, but the umbilical cord for array CGH (aCGH) revealed a 422 kb deletion at 15q13.3. Peripheral blood of the parents for aCGH showed a 1.1 Mb deletion at 21q21.1 in the mother’s sample, and the same deletion at 15q13.3 was detected in the father’s blood. In case 2, NIPT showed a 1.5 Mb deletion at 22q11.21, but aCGH of amniocytes revealed a 1.377 Mb duplication rather than a 1.5 Mb deletion at 22q11.21. Furthermore, aCGH analysis of the parental blood revealed a 647 kb deletion at 22q11.21 in the mother and a 2.8 Mb duplication of 22q11.21 in the father.

Conclusions

Our findings not only highlight the significance of diagnostic testing following a positive cfDNA sequencing result but also the necessity for additional analytical and clinical validation before routine use in practice.
Exome sequencing study revealed novel susceptibility loci in subarachnoid hemorrhage (SAH)
Authors: Hao Xiwa , Pang Jiangxia , Li Ruiming , Lv Lin , Liu Guorong , Li Yuechun , Cheng Guojuan , Zhang Jingfen
Published: May 2020

Aim

To expand our current understanding of the genetic basis of subarachnoid hemorrhage (SAH), and reveal the susceptibility genes in SAH risk.

Methods

We conducted whole-exome sequencing (WES) in a cohort of 196 individuals, including 94 SAH patients and 94 controls, as well as 8 samples that belong to two pedigrees. Systematically examination for rare variations (through direct genotyping) and common variations (through genotyping and imputation) for SAHs were performed in this study.

Results

A total of 16,029 single-nucleotide polymorphisms (SNPs) and 108,999 short indels were detected in all samples, and among them, 30 SNPs distributed on 17 genes presented a strong association signal with SAH. Two novel pathogenic gene variants were identified as associated risk loci, including mutation in TPO and PALD1. The statistical analysis for rare, damaging variations in SAHs identified several susceptibility genes which were involved in degradation of the extracellular matrix and transcription factor signal pathways. And 25 putative pathogenic genes for SAH were also identified basic on functional interaction network analysis with the published SAH-associated genes. Additionally, pedigree analysis revealed autosomal dominant inheritance of pathogenic genes.

Conclusion

Systematical analysis revealed a key role for rare variations in SAH risk and discovered SNPs in new complex loci. Our study expanded the list of candidate genes associated with SAH risk, and will facilitate the investigation of disease-related mechanisms and potential clinical therapies.
Decision support tool and suggestions for the development of guidelines for the helicopter transport of patients with COVID-19
Authors: Bredmose Per P. , Diczbalis Monica , Butterfield Emma , Habig Karel , Pearce Andrew , Osbakk Svein Are , Voipio Ville , Rudolph Marcus , Maddock Alistair , O’Neill John
Published: May 2020

The novel coronavirus SARS-CoV2 emerged in December 2019 and is now pandemic. Initial analysis suggests that 5% of infected patients will require critical care, and that respiratory failure requiring intubation is associated with high mortality.

Sick patients are geographically dispersed: most patients will remain in situ until they are in need of critical care. Additionally, there are likely to be patients who require retrieval for other reasons but who are co-incidentally infected with SARS-CoV-2 or shedding virus.

The COVID-19 pandemic therefore poses a challenge to critical care retrieval systems, which often depend on small teams of specialists who live and work together closely. The infection or quarantining of a small absolute number of these staff could catastrophically compromise service delivery.

Avoiding occupational exposure to COVID-19, and thereby ensuring service continuity, is the primary objective of aeromedical retrieval services during the pandemic. In this discussion paper we collaborated with helicopter emergency medical services(HEMS) worldwide to identify risks in retrieving COVID-19 patients, and develop strategies to mitigate these.

Simulation involving the whole aeromedical retrieval team ensures that safety concerns can be addressed during the development of a standard operating procedure. Some services tested personal protective equipment and protocols in the aeromedical environment with simulation. We also incorporated experiences, standard operating procedures and approaches across several HEMS services internationally.

As a result of this collaboration, we outline an approach to the safe aeromedical retrieval of a COVID-19 patient, and describe how this framework can be used to develop a local standard operating procedure.
Hypertrophied reversed palmaris longus muscle (pseudotumor) of the forearm causing median nerve compression: a case report
Authors: Hashem Majdi , Alatassi Raheef , Narinder Kaushal , Emran Fawaz
Published: May 2020

Background

The palmaris longus muscle is considered one of the most anatomically variable muscles in the human body. Localized swelling of the forearm due to hypertrophy of the palmaris longus muscle is rare.

Case presentation

Here, we report a rare case of a 24-year-old Arab man who presented with a painful mass on his forearm with symptoms of median nerve compression. A full radiological assessment was performed, and he was treated conservatively.

Conclusion

This case confirmed that a hypertrophied palmaris longus muscle can be the cause of swelling on the forearm and should always be considered in the differential diagnosis. With this report, we aimed to increase awareness regarding the unusual variations of palmaris longus muscle and the importance of using radiological investigations to establish a diagnosis.
Integration of new moving object segmentation and classification techniques using optimal salp swarm-based feature fusion with linear multi k-SVM classifier
Authors: G. Jemilda , S. Baulkani
Published: May 2020

The feature extraction technique is applied on least enclosing rectangle (LER) of the segmented object to increase the processing speed. The main intuition of this salp swarm algorithm relays on reducing the computational load of the proposed classifier by removing the repetitive and unrelated features from the feature vector. Also, increased training samples of similarly shaped classes when applied on the classifier can generate the misclassification results. Thus, a new layered kernel-based support vector machine (k-SVM) classifier is developed by means of integrating the k-neural network classifier and layered SVM classifier. Because of the high dimensional features, a difficulty occurs in the application of a single classifier. In order to ease the computational load, this multi classifier is integrated with a shadow elimination technique to classify the object categories of intelligent transportations system such as motorcycles, bicycles, cars, and pedestrians.
European ceramic technology in the Far East: enamels and pigments in Japanese art from the 16th to the 20th century and their reverse influence on China
Authors: Montanari Riccardo , Murakami Nobuyuki , Colomban Philippe , Alberghina Maria Francesca , Pelosi Claudia , Schiavone Salvatore
Published: May 2020

The production of Japanese enamels for porcelain decoration was thought to have originated from the direct and exclusive influence of Chinese potters who moved to Japan during the chaotic Ming to Qing dynastic change in 1644. Recent systematic studies have identified, for the first time, the crucial influence of Jesuit missionaries on pigment and enamel production in Japan from the late 16th-century. In particular, such first encounter laid the foundation for the continued influence exerted by European technology on Japanese art throughout the centuries. The present study has further identified European enamels used for the decoration of polychrome wares fired in Arita, the porcelain production center of Japan. This continued exchange not only marked the Edo period, but also extended into the twentieth century. For the first time, the lack of written records regarding the use of western pigments for enamel production caused by the persecutions of European and Japanese Christians has been overcome in the work herein presented. The nature of the imported materials has been firmly identified and characterized. The analytical results (EDXRF and Raman) have finally revealed how western technology and materials not only kept influencing Japanese art during the isolation (sakoku) period, but also accompanied the strong westernization process that marked Japanese history from the late nineteenth century. Moreover, the significant reverse influence of Japanese-made enamels on Chinese polychrome porcelain production in the late Qing and twentieth century has been fully identified for the first time. Furthermore, results show that the shift of the Pb mode of lead antimonate (Naples Yellow) is affected by the firing temperature for enamel decoration, and that this characteristic, along with the chemical composition, enables the identification of the origin and manufacture period of the yellow enamel.
Soft optical metamaterials
Authors: Chen Yixin , Ai Bin , Wong Zi Jing
Published: May 2020

Optical metamaterials consist of artificially engineered structures exhibiting unprecedented optical properties beyond natural materials. Optical metamaterials offer many novel functionalities, such as super-resolution imaging, negative refraction and invisibility cloaking. However, most optical metamaterials are comprised of rigid materials that lack tunability and flexibility, which hinder their practical applications. This limitation can be overcome by integrating soft matters within the metamaterials or designing responsive metamaterial structures. In addition, soft metamaterials can be reconfigured via optical, electrical, thermal and mechanical stimuli, thus enabling new optical properties and functionalities. This paper reviews different types of soft and reconfigurable optical metamaterials and their fabrication methods, highlighting their exotic properties. Future directions to employ soft optical metamaterials in next-generation metamaterial devices are identified.
Transverse colon perforation in the mediastinum after esophagectomy: a case report
Authors: Konno-Kumagai Takuro , Sakurai Tadashi , Taniyama Yusuke , Sato Chiaki , Takaya Kai , Ito Ken , Kamei Takashi
Published: May 2020

Background

While anastomotic leakage, recurrent laryngeal nerve paralysis, and pneumonia are well-known complications of esophagectomy, the incidence of hiatal hernia after esophagectomy for carcinoma has been reported to only be between 0.6 and 10%. We report a very rare case of hiatal hernia with transverse colon rupture in the mediastinum after esophagectomy in a 65-year-old woman.

Case presentation

The patient underwent definitive chemoradiotherapy for clinical stage IIA esophageal squamous cell carcinoma and salvage esophagectomy with gastric tube reconstruction through a posterior mediastinum route for residual carcinoma. Three years after the initial surgery, two metastatic nodules in the lateral and posterior segments of the liver were detected on follow-up CT and were treated with oral anticancer drugs. After 6 months, the patient was readmitted for anorexia. Upon admission, computed tomography revealed an ileus caused by a hiatal hernia. Emergent operative repair was performed; an incarcerated herniation of the transverse colon was perforated in the mediastinum, and partial transverse colon resection and colostomy were performed. Intensive care was required to control septic shock after surgery, and the patient was discharged on the 53rd postoperative day.

Conclusions

Cases of hiatal hernia with digestive tract prolapsing into the mediastinum after esophagectomy with reconstruction through posterior mediastinum are rare but potentially life-threatening complications.
Computational modeling and ligand-based design of some novel hypothetical compound as prominent inhibitors against Mycobacterium tuberculosis
Authors: Adeniji Shola Elijah , Adalumo Olajumoke Bosede
Published: May 2020

Background

Time consumed and expenses in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug-resistant strain Mycobacterium tuberculosis (TB). To solve the above problem, quantitative structure activity relationship (QSAR) is a recent approach developed to discover novel agents with better biological activity against M. tuberculosis.

Results

A validated QSAR model was developed in this study to predict the biological activities of some anti-tubercular compounds and to design new hypothetical drugs is influenced with the molecular descriptors, AATS7s, VR1_Dzi, VR1_Dzs, SpMin7_Bhe, and TDB8e, which has been validated through internal and external validation test. Prior to high anti-tubercular activity of the lead compound, compound 17 served as a template structure to design compounds with improved activity. Among the compounds designed, compounds 17i, 17j, and 17n were observed with improved anti-tubercular activities which ranges from 8.8981 to 9.0377 pBA.

Conclusion

The outcome of this research is recommended for pharmaceutical and medicinal chemists to synthesis and carry out an in vivo and in vitro screening for the proposed designed compounds in order to substantiate the computational findings.
KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.
Authors: Cortes Javier , Cescon David W. , Rugo Hope S. , Nowecki Zbigniew , Im Seock-Ah , Yusof Mastura Md , Gallardo Carlos , Lipatov Oleg , Barrios Carlos Henrique , Holgado Esther , Iwata Hiroji , Masuda Norikazu , Torregroza Otero Marco , Gokmen Erhan , Loi Sherene , Guo Zifang , Zhao Jing , Aktan Gursel , Karantza Vassiliki , Schmid Peter
Published: May 2020

1000

Background: Pembrolizumab (pembro) monotherapy showed promising antitumor activity and manageable safety in patients (pts) with metastatic TNBC in KEYNOTE-012, -086 and -119. KEYNOTE-355 (ClinicalTrials.gov, NCT02819518) compared pembro + chemotherapy (chemo) vs placebo (pbo) + chemo for previously untreated locally recurrent inoperable or metastatic TNBC. Methods: Pts with ≥6 mo DFI were randomized 2:1 to pembro + chemo (nab-paclitaxel; paclitaxel; or gemcitabine/carboplatin) or pbo + chemo for up to 35 administrations of pembro/pbo or until progression/intolerable toxicity. Pts were stratified by chemo type (taxane vs gemcitabine/carboplatin), PD-L1 status (CPS ≥1 vs <1), and prior (neo)adjuvant treatment with same-class chemo (yes vs no). Dual primary endpoints are PFS (RECIST v1.1, blinded independent central review) and OS by tumor PD-L1 expression (CPS ≥10 and ≥1) and in all pts. PFS was estimated using the Kaplan-Meier method. Stratified log-rank tests were used to assess treatment group differences. HR and 95% CIs were based on a stratified Cox regression model. AEs were monitored throughout the study and graded per NCI CTCAE v4.0. Results: As of Dec 11 2019, median follow-up was 17.5 mo for pembro + chemo (n=566) and 15.5 mo for chemo (n=281). Pembro + chemo significantly improved PFS vs chemo alone in pts with CPS ≥10 tumors (Table), meeting one of the protocol-defined primary objectives. Although the boundary for a statistically significant benefit of pembro + chemo in pts with CPS ≥1 tumors was not met and formal testing in ITT was not performed, the pembro treatment effect increased with PD-L1 enrichment (Table). OS follow-up is ongoing. Grade 3-5 treatment-related AE rates were 68.1% with pembro + chemo (2 deaths) vs 66.9% with chemo (0 deaths); rates of grade 3-4 immune-mediated AEs and infusion reactions were 5.5% vs 0%. Clinical trial information: NCT02819518 . Conclusion: Pembro combined with several chemo partners showed a statistically significant and clinically meaningful improvement in PFS vs chemo alone in pts with previously untreated locally recurrent inoperable or metastatic TNBC whose tumors expressed PD-L1 (CPS ≥10). Pembro + chemo was generally well tolerated, with no new safety concerns. [Table: see text]
Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
Authors: Sarnaik Amod , Khushalani Nikhil I. , Chesney Jason Alan , Lewis Karl D. , Medina Theresa Michelle , Kluger Harriet M. , Thomas Sajeve Samuel , Domingo Musibay Evidio , Pavlick Anna C. , Whitman Eric D. , Martin-Algarra Salvador , Corrie Philippa Gail , Lutzky Jose , Hamid Omid , Wu Renee , Shi Wen , Fardis Maria , Weber Jeffrey S. , Larkin James M. G. , Kirkwood John M.
Published: May 2020

10006

Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) leverages and enhances the body’s natural defense against cancer and has shown durable responses in heavily pretreated melanoma patients. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of efficacy & safety of lifileucel in patients with unresectable metastatic melanoma who have progressed on checkpoint inhibitors and BRAF/MEK inhibitors, if BRAFv600 mutant. We report on Cohort 2 (N = 66) patients who have received TIL. Tumors were resected at local institutions, processed in central GMP facilities for TIL production, manufactured, cryopreserved & shipped back to sites in a 22-day process. Therapy consisted of one week of lymphodepletion, a single lifileucel infusion, and up to 6 IL-2 doses. ORR was based on RECIST v1.1 by investigator assessment. Data cutoff was Feb 2, 2020. Results: Baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), high baseline tumor burden (106 mm mean target lesion sum of diameters), 44% liver/brain lesions, 40.9% LDH > ULN. ORR by investigator was 36.4% (2 CR, 22 PR) and DCR was 80.3%. Mean time to response was 1.9 months (range: 1.3-5.6). After a median study follow-up of 17.0 months, median DOR (mDOR) was still not reached. Six responders have progressed, 2 have died and 2 started other anti-cancer therapy without progression. The adverse event profile was consistent with the underlying advanced disease and the lymphodepletion and IL-2 regimens. Additional follow-up data will be available for presentation. Conclusions: Lifileucel treatment results in a 36.4% ORR and mDOR was not reached at 17.0 months of median study follow up in a heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD1 and BRAF/MEK inhibitors, if BRAFv600 mutant. Clinical trial information: NCT02360579.