bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and performance of catheter ablation with zero-fluoroscopy approach for regular supraventricular tachycardia in patients with structural and/or congenital heart disease
Authors: Morka Aleksandra , Śledź Janusz , Deutsch Karol , Ludwik Bartosz , Zagrodzka Magdalena , Szydłowski Lesław , Stec Sebastian
Published: October 2019

Patients with structural heart disease (SHD) are more difficult to ablate than those with a structurally healthy heart. The reason may be technical problems. We compared periprocedural data in unselected patients (including SHD group) recruited for zero-fluoroscopy catheter ablation (ZF-CA) of supraventricular arrhythmias (SVTs).

Consecutive adult patients with atrioventricular nodal reentry tachycardia (AVNRT), accessory pathways (AP), atrial flutter (AFL), and atrial tachycardia (AT) were recruited. A 3-dimensional electroanatomical mapping system (Ensite Velocity, NavX, St Jude Medical, Lake Bluff, Illinois) was used to create electroanatomical maps and navigate catheters. Fluoroscopy was used on the decision of the first operator after 5 minutes of unresolved problems.

Of the 1280 patients ablated with the intention to be treated with ZF approach, 174 (13.6%) patients with SHD (age: 58.2 ± 13.6; AVNRT: 23.9%; AP: 8.5%; AFL: 61.4%; and AT: 6.2%) were recruited. These patients were compared with the 1106 patients with nonstructural heart disease (NSHD) (age: 51.4 ± 16.4; AVNRT: 58.0%; AP: 17.6%; AFL: 20.7%; and AT: 3.7% P ≤ .001). Procedural time (49.9 ± 24.6 vs 49.1 ± 23.9 minutes, P = .55) and number of applications were similar between groups (P = 0.08). The rate of conversion from ZF-CA to fluoroscopy was slightly higher in SHD as compared to NSHD (13.2% vs 7.8%, P 
= .02) while the total time of fluoroscopy and radiation doses were comparable in the group of SHD and NSHD (P = .55; P = .48).

ZF-CA is feasible and safe in majority of patients with SHD and should be incorporated into a standard approach for SHD; however, the procedure requires sufficient experience.
Thoracic myelopathy caused by an extremely rare aberrant epidural ligament
Authors: Hirai Takashi , Yoshii Toshitaka , Tanimoto Takahiro , Ushio Shuta , Sasaki Shinichi , Inose Hiroyuki , Yuasa Masato , Okawa Atsushi
Published: October 2019

Rationale:

The meningovertebral ligaments are a group of tissues that connect the dura and the vertebral bone. Abnormal fibrous ligaments in the canal space, which are essentially different from these ligaments, have been identified and their presence very rarely results in spinal disorder.

Patient concerns:

A 20-year-old Mongolian woman had developed persistent headache at 15 years of age. She then became unable to run fast when she was 19 years old and had progressively declining ability to move. She complained of back pain and unstable gait 6 months prior to presentation. Physical examination revealed exaggerated deep tendon reflexes in the lower extremities and decreased proximal leg muscle strength bilaterally.

Diagnoses:

Magnetic resonance imaging (MRI) revealed abnormal bands compressing the spinal cord at the T10/11 level, with large epidural lipomatosis dorsal to the dural tube.

Intervention:

To decompress the cord, posterior laminectomy for T3-L3 and removal of the heterotopic ligaments were performed with T8-L1 posterior fusion.

Outcomes:

Sufficient decompression of the cord was noted on postoperative MRI at the affected segments. The patient could subsequently walk without a cane and headache resolved immediately after the operation.

Lessons:

The presence of an aberrant epidural band is a rare pathologic state that often coexists with a surrounding lipomatosis and can lead to spinal cord compression. Removal of the band is a promising treatment for myelopathy caused by the compressive lesion.
Preoperative prolonged fasting causes severe metabolic acidosis
Authors: Zhou WenQin , Luo LinLi
Published: October 2019

Rationale:

Preoperative prolonged fasting may cause starvation ketoacidosis. Herein, we report of a case of starvation ketoacidosis due to long-term fasting before surgery.

Patient concerns:

We report of a case of metabolic acidosis due to prolonged fasting in a previously healthy 44-year-old woman during a total laparoscopic hysterectomy. Hyperventilation was observed to occur when the surgery was completed. Metabolic acidosis and hypoglycemia were demonstrated by blood gas analysis of the radial artery.

Diagnosis:

Metabolic acidosis.

Interventions:

The patient received sodium bicarbonate and 5% glucose fluid at the end of the surgery.

Outcomes:

The tracheal tube was successfully removed when the tidal volume of the patient returned to normal after the therapy. However, the patient suffered pulmonary edema when she was transferred to the intensive care unit (ICU). With treatments with furosemide and sodium bicarbonate, acidosis and pulmonary edema were completely corrected at 8 hours after the surgery. On the second day after the surgery, the patient suffered nausea and vomiting. Nausea and vomiting were not completely relieved on the sixth day after the operation; therefore, the patient was transferred to the Department of Gastroenterology for further therapy.

Lessons:

This case suggests that although the concept of enhanced recovery after surgery (ERAS) has been adopted by most physicians because of its positive outcomes, the issue of prolonged fasting still exists, and such patients may be exposed to the risk of starvation ketoacidosis.
Clinical study of ultrasound-guided transversus abdominis plane block for analgesia after cesarean section
Authors: Gao Yuanchao , Guo Mengzhuo , Du Chunyan , Zhang Haijing , Zhang Huan
Published: October 2019

Background:

Patient-controlled intravenous analgesia (PCIA) and patient-controlled epidural analgesia are 2 common methods of maintaining analgesia after cesarean section. In recent years, transversus abdominis plane block (TAPB) has been gradually applied clinically to reduce opioid analgesics and has achieved good results. Therefore, we performed this study to compare the efficacy and side effects of TAPB and PCIA in analgesia after cesarean section.

Methods:

One hundred patients who underwent cesarean section were randomly classified into 2 groups. Following surgery, one group underwent ultrasound-guided TAPB and the other group underwent PCIA. Pain intensity according to the visual analog scale (VAS; 0 for no pain and 10 for severe intolerable pain) was assessed at 2, 4, 6, 8, 12, and 24-hour postsurgery in both groups. The postoperative complication rate and patient satisfaction were also measured.

Results:

No significant differences were found in the VAS scores between the groups (P > .05). However, the incidence of postoperative complications in the TAPB group was significantly lower than that in the PCIA group (P < .05). Furthermore, patient satisfaction in the TAPB group was significantly higher than that in the PCIA group (P < .05).

Conclusion:

This study demonstrated that ultrasound-guided TAPB can achieve the same analgesic effect as PCIA after cesarean section but with even higher patient satisfaction.
Dosimetric comparison of incidental radiation to the internal mammary nodes after breast-conserving surgery using 3 techniques-inverse intensity-modulated radiotherapy, field-in-field intensity-modulated radiotherapy, and 3-dimensional conformal radiotherapy
Authors: Song Yuanfang , Yu Ting , Wang Wei , Li Jianbin , Sun Tao , Qiu Pengfei , Xu Min , Shao Qian
Published: October 2019

Background:

The study aimed to evaluate and compare the dosimetric parameters of incidental irradiation to internal mammary node (IMN) from inverse intensity-modulated radiotherapy (I-IMRT) and field-in-field IMRT (F-IMRT), and 3-dimensional conformal radiotherapy (3D-CRT) in patients after breast-conservation surgery (BCS).

Methods:

Eighty-four patients with BCS were selected. The breast, tumor bed, and IMN, including intercostal spaces (ICS) 1 to 3, were contoured. Three plans were generated. The prescription doses for the breast and tumor bed were 50.4 Gy/28 F and 60.2 Gy/28 F, respectively. If there was no tumor bed boost, patient was treated with 50 Gy/25 F for the whole breast only. The IMN was not included in planning target volume.

Results:

The median mean dose (Dmean) of the IMNtotal (ICS 1–3) was 2740.2 cGy, 2973.9 cGy, and 2951.4 cGy for I-IMRT, F-IMRT, and 3D-CRT, respectively. Differences were not detected between any of the plans. After separating ICS 1 to 3 for further analysis, neither of the Dmean of ICS 1 to 2 was significantly different between the plans. However, for ICS 3, the median Dmean was highest for I-IMRT, and those for 3D-CRT and F-IMRT were not significantly different. After separating the 3 techniques for further analysis, the median Dmean was highest in ICS 3 and lowest in ICS 1 for all the 3 techniques.

Conclusion:

All 3 techniques failed to attain an adequate dose to cure subclinical disease, and there were no significant differences among the 3 techniques. It is risky to avoid IMN irradiation (IMNI) using any of the 3 techniques during whole-breast radiotherapy in women with indications for elective IMNI. However, in era of systematic therapy, whether the incidental dose could meet clinical acquirements needs further follow-up.
Successful treatment of refractory edema with traditional herbal medicine
Authors: Lee Gayoung , Cho Jung-Hyo , Son Chang-Gue , Lee Namhun
Published: October 2019

Rationale:

Refractory edema is characterized by persistent swelling which does not react to diuretic use and sodium restriction. Traditional herbal medicine, Gwack Rhyung Tang and Chunggan extract effectively treated refractory lower limb edema caused by cirrhosis and improved liver function.

Patient concerns:

A 64-year-old male patient with a history of hypertension, diabetes mellitus, hepatic encephalopathy, and cellulitis presented lower limb edema which did not react to diuretics for more than 7 months.

Diagnoses:

Refractory edema caused by cirrhosis.

Interventions:

The patient was treated for 25 days using Gwack Rhyung Tang and Chunggan extract.

Outcomes:

Loss of body weight, decrease in circumferences of both lower limb and improvement of liver function biochemistry results are checked. There was no recurrence or aggravation of the condition up to 3 weeks of follow-up periods.

Lessons:

Traditional herbal medicine can be an effective alternative for refractory edema due to cirrhosis with improving liver function.
Coexistence of Fabry disease with IgM nephropathy
Authors: Wu Huizhen , Behera Tapas Ranjan , Gong Jianguang , Shen Quanquan
Published: October 2019

Rationale:

Coexistence of Fabry disease and IgM nephropathy is rare. The varying severity and unapparent clinical manifestation of Fabry disease makes it difficult to recognize when coexisting with another more prevalent cause of nephropathy requiring electron microscopy and genetic testing to confirm their coexistence.

Patient concerns:

A 54-year-old female presented with proteinuria without any clinical signs or family history of Fabry disease.

Diagnoses:

Immunostaining of the renal biopsy identified mesangial IgM deposition diagnosing it as IgM nephropathy. The light microscopy indicated prominent vacuolization of podocytes. Further examination of toluidine blue stained semi-thin sections and electron microscopy revealed blue bodies and myelin bodies in the cytoplasm of podocytes, respectively. Mutation analysis detected missense mutation establishing the diagnosis of coexisting Fabry disease.

Interventions:

The patient was treated with angiotensin-converting enzyme inhibitors. Enzyme replacement therapy was not administered due to financial constraints.

Outcomes:

After 2 months of treatment the patient demonstrated urine protein to creatinine ratio of 0.21 g/g.

Lessons:

Identifying coexistence of Fabry disease with other nephropathy requires meticulous pathologic investigations including electron microscopy especially when Fabry disease presents with atypical phenotype.
An unusual case of pediatric-type follicular lymphoma
Authors: Zhang Hanyu , Sun Shuai , Zhang Biru , Yang Hongyu
Published: October 2019

Rationale:

Pediatric-type follicular lymphoma (PTFL) is a rare neoplasm with features that differ from those of adult-type follicular lymphoma. Compared to patients with adult-type follicular lymphoma, PTFL patients often show an excellent response. Preoperative diagnosis is challenging and, therefore, an accurate diagnosis is based on the findings of postoperative pathological examination and immunohistochemistry.

Patient concerns:

A 13-year-old boy presented with a slow-growing mass on the right side of his neck.

Diagnoses:

The patient was diagnosed with PTFL based on the findings of histopathological examination and immunohistochemistry.

Intervention:

The mass was completely resected.

Outcomes:

After 12 months of postoperative follow-up, the patient achieved good recovery without recurrence.

Lessons:

The optimal treatment for PTFL has not yet been defined. However, patients with PTFL always show satisfactory prognoses, regardless of treatment strategy (targeted radiotherapy, multiagent chemotherapy, or “watch and wait” strategy). Clinically, pathological and immunohistochemical analyses are necessary in the diagnoses of PTFL cases, especially for distinguishing PTFL from reactive follicular hyperplasia, to avoid unnecessary treatment.
Mushroom intoxication, a fatal condition in Romanian children
Authors: Mărginean Cristina Oana , Meliţ Lorena Elena , Mărginean Maria Oana
Published: October 2019

Rationale:

Approximately 5000 species of wild mushroom are reported worldwide, of which 100 are documented as poisonous and <10 are fatal. The clinical picture of patients with wild mushroom intoxication depends mostly on the type of ingested mushroom, ranging from mild gastrointestinal symptoms to organ failure and death.

Patient concerns:

We report 2 children, sister and brother admitted in our clinic for gastrointestinal symptoms: abdominal pain, nausea, vomiting, and diarrhea after wild mushroom ingestion.

Diagnosis:

The laboratory tests revealed hepatic cytolysis syndrome, hyperbilirubinemia, impaired coagulation status, hypoalbuminemia, hypoglycemia, and electrolytic unbalances in both cases. Abdominal ultrasound showed hepatomegaly and ascites.

Intervention:

After admission, both cases received penicillin by vein, activated charcoal, liver protectors, glucose, and electrolytes perfusions. Nevertheless, their status worsened and required the transfer to the pediatric intensive care unit for appropriate supportive measure. Therefore, therapeutic plasma exchange was initiated along with N-acetyl cysteine and hemostatic drugs.

Outcomes:

Despite all these therapeutic interventions, both cases developed hepatorenal syndrome and died after a couple of days from ingestion.

Lessons:

Mushroom poisoning remains a public health problem in developing countries. Preventable strategies and education regarding the consumption of wild type mushrooms are essential for decreasing the morbidity and mortality rates in these areas.
Biphenotypic Differentiation of Pancreatic Cancer in 3-Dimensional Culture
Authors: Matsushita Yoshihisa , Smith Barbara , Delannoy Michael , Trujillo Maria A. , Chianchiano Peter , McMillan Ross , Kamiyama Hirohiko , Liang Hong , Thompson Elizabeth D. , Hruban Ralph H. , Matsui William , Wood Laura D. , Roberts Nicholas J. , Eshleman James R.
Published: October 2019

Objective

Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the United States. Improved characterized models of PDAC are needed for drug screening.

Methods

We grew 4 established pancreatic cancer cell lines in hanging drop cultures to produce spheroids. We also grew organoids from explanted xenografted PDAC and surgically resected primary PDAC. We performed transmission and scanning electron microscopy and compared findings with those of the normal pancreatic duct. We also performed single-cell cloning to determine the potential options for differentiation.

Results

Spheroids contained tight junctions and desmosomes but lacked zymogen granules, as expected. The former features were present in normal pancreatic duct but absent from PDAC cell lines grown in standard 2-dimensional culture. Spheroids functionally excluded macromolecules in whole mounts. Cells on the surface of PDAC spheroids were carpeted by microvilli except for rare cells with prominent stereocilia. Carpets of microvilli were also seen in low passage organoids produced from xenografts and surgically resected human PDAC, in addition to normal human pancreatic duct. We performed single-cell cloning and resulting spheroids produced both cell phenotypes at the same approximate ratios as those from bulk cultures.

Conclusions

Pancreatic cancer spheroids/organoids are capable of biphenotypic differentiation.
Case Series: Slight Intraocular Lens Malpositioning as a Potential Cause of Vision Loss
Authors: Rong Xianfang , Miao Ao , Yu Jifeng , Du Yu , He Wenwen , Lu Yi , Zhu Xiangjia
Published: October 2019

SIGNIFICANCE

The cases illustrate an insidious cause of decreased visual acuity after cataract surgery.

PURPOSE

The purpose of this study was to identify cases of postoperative vision loss caused by slight intraocular lens (IOL) malpositioning after cataract surgery.

CASE REPORTS

Three patients presented with visual acuity decreased after cataract surgery. Silt-lamp examination before mydriasis revealed no abnormalities in two of the patients; mild IOL inferonasal decentration was found by the trifocal IOL diffraction ring in the third patient. Manifest refraction of these patients showed remarkable astigmatism with low corneal astigmatism. After pupil dilation, slight IOL decentration and tilt were observed in all patients, which were further confirmed using the Scheimpflug imaging system. Wavefront aberrometry showed a high level of ocular higher-order aberrations, most of which were derived from intraocular aberrations.

CONCLUSIONS

Inconspicuous IOL malpositioning is one of the reasons responsible for decreased vision acuity after cataract surgery, which may not be easily identified by slit-lamp examination. High astigmatism and ocular higher-order aberrations derived from malpositioned IOL can be important clues.
Does a Hand Strength–Focused Exercise Program Improve Grip Strength in Older Patients With Wrist Fractures Managed Nonoperatively?
Authors: Nguyen Antony , Vather Mehr , Bal Gobind , Meaney Donna , White Megan , Kwa Myles , Sungaran Jai
Published: October 2019

Objective

Distal radius fractures in the older population significantly impair grip strength. The aim of the study was to investigate whether a hand strength focused exercise program during the period of immobilization for nonoperatively managed distal radius fractures in this population improved grip strength and quality of life.

Design

This is a single-center randomized controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Fifty-two patients older than 60 yrs who experienced distal radius fractures managed nonoperatively with cast immobilization. The intervention group (n = 26) received a home hand strength–focused exercise program from 2 and 6 wks after injury while immobilized in a full short arm cast. The control group (n = 26) performed finger range of motion exercises as per protocol. Primary outcome was grip strength ratio of injured arm compared with uninjured arm. Secondary outcome included functional scores of the 11-item shortened version of the Disabilities of the Arm, Shoulder and Hand. Outcomes were measured at 2, 6, and 12 wks after injury.

Results

The intervention group significantly improved grip strength ratio at both 6 and 12 wks (6 wks: 40% vs 25%, P = 0.0044, and 12 wks: 81% vs 51%, P = 0.0035). The intervention group improved the 11-item Disabilities of the Arm, Shoulder and Hand score at 12 wks; however, this was not statistically significant (25 vs 40, P = 0.066).

Conclusions

A hand strength–focused exercise program for elderly patients with distal radius fractures while immobilized significantly improved grip strength.
Arm Subscore of Motricity Index to Predict Recovery of Upper Limb Dexterity in Patients With Acute Ischemic Stroke
Authors: Malmut Laura , Lin Chen , Srdanovic Nina , Kocherginsky Masha , Harvey Richard L. , Prabhakaran Shyam
Published: October 2019

Objective

The aim of this study was to determine whether the arm subscore of the Motricity Index 1 wk after stroke can predict recovery of upper limb function according to the Action Research Arm Test before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up.

Design

This was a prospective cohort study of patients with acute ischemic stroke admitted to a single acute care hospital and affiliated inpatient rehabilitation facility between 2016 and 2018. Upper limb dexterity of the impaired limb was assessed using the arm subscore of the Motricity Index and Action Research Arm Test. Receiver operating characteristic curve analysis was used to determine optimal cutoffs of the initial arm subscore of the Motricity Index for a good functional outcome defined as Action Research Arm Test score of 45 or higher.

Results

Ninety-five patients were evaluated at median 6, 26, and 98.5 days after stroke. The median (interquartile range) arm subscore of the Motricity Index at 1 wk was 77 (20.3–93). The median (interquartile range) Action Research Arm Test scores before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up were 33 (3.5–52) and 52 (34–55.8), respectively. The optimal arm subscore of the Motricity Index to predict Action Research Arm Test score of 45 or higher before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up were 71 and 58, respectively.

Conclusions

Early arm subscore of the Motricity Index at 1 wk predicts upper limb functional capacity before inpatient rehabilitation facility discharge and at 3-mo outpatient follow-up.
Comparison of Hamra's and Mendelson's Models of Midface Lift
Authors: Choi Jeongho , Hwang Kun
Published: October 2019

The aim of this study was to compare Hamra's and Mendelson's models of midface lift.

The terms “Hamra ST” and “Mendelson BC” were used to search PubMed, yielding 35 and 48 papers, respectively. Of the 83 abstracts, 55 were excluded and 28 full papers discussing midface lift were reviewed. Among those 28 papers, 13 were excluded because they did not have sufficient content. Among the 15 full texts, 5 mined papers were added. Thereafter, 20 papers were analyzed.

Hamra's description of his surgical technique changed twice. In 1990 (The Deep-Plane Rhytidectomy), he wrote that he performed Skoog-type subsuperficial muscular aponeurotic system (SMAS) dissection to the nasolabial fold. In 1992 (Composite Rhytidectomy), however, he cited a paper insisting that the SMAS does not exist in the cheek area. He wrote that his deep-plane rhytidectomy was not a sub-SMAS procedure, stating that he dissected the cheek fat that is attached to the zygomaticus major, then repositioned the skin. This was a substantially different explanation of the dissection plane. In 1997, he stated that instead of dividing the orbicularis oculi muscle from the zygomaticus major and minor, he elevated them together in a flap. Thus, his method returned to the sub-SMAS plane. Mendelson introduced the concepts of the prezygomatic space, orbicularis-retaining ligament, and zygomatic-retaining ligament, and proposed an anatomical model.

If the authors explain Hamra's zygorbicular dissection using Mendelson's model, the dissection starts just beneath the roof of the prezygomatic space, traverses the floor, and then releases the zygomatic ligament (lower boundary of the space). The authors should consider the necessity and riskiness of this release.
Variation in genome content and predatory phenotypes between Bdellovibrio sp. NC01 isolated from soil and B. bacteriovorus type strain HD100
Authors: Williams Laura E. , Cullen Nicole , DeGiorgis Joseph A. , Martinez Karla J. , Mellone Justina , Oser Molly , Wang Jing , Zhang Ying
Published: October 2019

Defining phenotypic and associated genotypic variation among

Bdellovibrio

may further our understanding of how this genus attacks and kills different Gram-negative bacteria. We isolated

Bdellovibrio

sp. NC01 from soil. Analysis of 16S rRNA gene sequences and average amino acid identity showed that NC01 belongs to a different species than the type species bacteriovorus. By clustering amino acid sequences from completely sequenced

Bdellovibrio

and comparing the resulting orthologue groups to a previously published analysis, we defined a ‘core genome’ of 778 protein-coding genes and identified four protein-coding genes that appeared to be missing only in NC01. To determine how horizontal gene transfer (HGT) may have impacted NC01 genome evolution, we performed genome-wide comparisons of

Bdellovibrio

nucleotide sequences, which indicated that eight NC01 genomic regions were likely acquired by HGT. To investigate how genome variation may impact predation, we compared protein-coding gene content between NC01 and the

B. bacteriovorus

type strain HD100, focusing on genes implicated as important in successful killing of prey. Of these, NC01 is missing ten genes that may play roles in lytic activity during predation. Compared to HD100, NC01 kills fewer tested prey strains and kills

Escherichia coli

ML35 less efficiently. NC01 causes a smaller log reduction in ML35, after which the prey population recovers and the NC01 population decreases. In addition, NC01 forms turbid plaques on lawns of

E. coli

ML35, in contrast to clear plaques formed by HD100. Linking phenotypic variation in interactions between

Bdellovibrio

and Gram-negative bacteria with underlying

Bdellovibrio

genome variation is valuable for understanding the ecological significance of predatory bacteria and evaluating their effectiveness in clinical applications.
Integrative modelling of the full-length human dehydrodolichyl diphosphate synthase using a hybrid computational and experimental approach
Authors: Barel Michal Lisnyansky , Lee Su Youn , Ki Ah Young , Kapelushnik Noa , Loewenstein Anat , Chung Ka Young , Schneidman-Duhovny Dina , Giladi Moshe , Newman Hadas , Haitin Yoni
Published: October 2019

Dehydrodolichyl diphosphate synthase (DHDDS) and Nogo-B receptor (NgBR) form the heteromeric human cis-prenyltransferase complex, synthesizing the precursor for the glycosyl carrier involved in N-linked protein glycosylation. In line with the important role of N-glycosylation in protein biogenesis, mutations in DHDDS, the catalytic subunit of the complex, were shown to result in human diseases. Importantly, well-characterized DHDDS homologs function as homodimers and not as heteromeric complexes. Moreover, DHDDS encompasses a C-terminal region, which does not converge with any known conserved domains. Therefore, despite the clinical importance of DHDDS, our understating of its structure-function relations remains poor. Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach. Our model suggests that the C-terminal domain of DHDDS forms a helix-loop-helix motif, tightly packed against the core catalytic cis-prenyltransferase domain. This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution. Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state. Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the human cis-prenyltransferase complex.
MetaSanity: An integrated, customizable microbial genome evaluation and annotation pipeline
Authors: Neely Christopher J , Graham Elaina D , Tully Benjamin J
Published: October 2019

As the importance of microbiome research continues to become more prevalent and essential to understanding a wide variety of ecosystems (e.g., marine, built, host-associated, etc.), there is a need for researchers to be able to perform highly reproducible and quality analysis of microbial genomes. MetaSanity incorporates analyses from eleven existing and widely used genome evaluation and annotation suites into a single, distributable workflow, thereby decreasing the workload of microbiologists by allowing for a flexible, expansive data analysis pipeline. MetaSanity has been designed to provide separate, reproducible workflows, that (1) can determine the overall quality of a microbial genome, while providing a putative phylogenetic assignment, and (2) can assign structural and functional gene annotations with varying degrees of specificity to suit the needs of the researcher. The software suite combines the results from several tools to provide broad insights into overall metabolic function and putative extracellular localization of peptidases and carbohydrate-active enzymes. Importantly, this software provides built-in optimization for “big data” analysis by storing all relevant outputs in an SQL database, allowing users to query all the results for the elements that will most impact their research.

Availability and implementation

MetaSanity is provided under the GNU General Public License v.3.0 and is available for download at https://github.com/cjneely10/MetaSanity. This application is distributed as a Docker image. MetaSanity is implemented in Python3/Cython and C++.

Supplementary information

Supplementary data are available below.
Epigenetic contributions to hemisphere asymmetry in healthy brain, aging, and Parkinson’s disease
Authors: Li Peipei , Ensink Elizabeth , Lang Sean , Marshall Lee , Schilthuis Meghan , Lamp Jared , Vega Irving , Labrie Viviane
Published: October 2019

Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson’s disease (PD), but its molecular determinants are unknown. Here, we determine epigenetic differences involved in hemispheric asymmetry in the healthy and the PD brain. Neurons of the healthy brain exhibit numerous hemispheric differences in DNA methylation, which affect genes implicated in neurodegenerative diseases. In PD patients, hemispheric asymmetry in DNA methylation is even greater and involves many PD risk genes. The lateralization of clinical PD symptoms involves epigenetic, transcriptional, and proteomic differences across hemispheres that affect neurodevelopment, immune activation, and synaptic transmission. During aging, healthy neurons show a progressive loss of hemispheric asymmetry in the epigenome, which is amplified in PD. For PD patients, a long disease course is associated with greater hemispheric asymmetry in neuronal epigenomes than a short disease course. Hemispheric differences in epigenetic gene regulation are prevalent in neurons and may affect the progression and symptoms of PD.
Scalable empirical mixture models that account for across-site compositional heterogeneity
Authors: Schrempf Dominik , Lartillot Nicolas , Szöllősi Gergely
Published: October 2019

Biochemical demands constrain the range of amino acids acceptable at specific sites resulting in across-site compositional heterogeneity of the amino acid replacement process. Phylogenetic models that disregard this heterogeneity are prone to systematic errors, which can lead to severe long branch attraction artifacts. State-of-the-art models accounting for across-site compositional heterogeneity include the CAT model, which is computationally expensive, and empirical distribution mixture models estimated via maximum likelihood (C10 to C60 models). Here, we present a new, scalable method EDCluster for finding empirical distribution mixture models involving a simple cluster analysis. The cluster analysis utilizes specific coordinate transformations which allow the detection of specialized amino acid distributions either from curated databases, or from the alignment at hand. We apply EDCluster to the HOGENOM and HSSP databases in order to provide universal distribution mixture (UDM) models comprising up to 4096 components. Detailed analyses of the UDM models demonstrate the removal of various long branch attraction artifacts and improved performance compared to the C10 to C60 models. Ready-to-use implementations of the UDM models are provided for three established software packages (IQ-TREE, Phylobayes, and RevBayes).
Relationship between neural phase-locked responses to speech and perception of speech in noise in young and older adults
Authors: Mai Guangting , Howell Peter
Published: October 2019

Auditory phase-locked responses are affected by aging and it has been proposed that this increases the challenges experienced during speech perception in noise (SPiN). However, this proposal lacks direct support. This issue was addressed by measuring speech-evoked phase-locked responses at subcortical (frequency-following responses, FFRs) and cortical (theta-band phase-locking, θ-PLV) levels, and studying the relationship between these phase-locked responses and SPiN (word report accuracies of sentences listened to in noise) in adults across a wide age-range (19-75 years old). It was found that: (1) FFR magnitudes declined with age after hearing loss was controlled for; (2) θ-PLV increased with age, suggesting cortical hyperexcitability in audition; (3) SPiN correlated positively with FFR magnitudes obtained in quiet and with θ-PLV obtained in noise, suggesting that impacts of aging (smaller FFR magnitudes and greater θ-PLV) on SPiN differ at subcortical and cortical levels. Thus, the current study provided evidence for different mechanisms at subcortical and cortical levels through which age affects speech-evoked phase-locked activities and SPiN.
Disentangling Sources of Gene Tree Discordance in Phylogenomic Datasets: Testing Ancient Hybridizations in Amaranthaceae s.l
Authors: Morales-Briones Diego F. , Kadereit Gudrun , Tefarikis Delphine T. , Moore Michael J. , Smith Stephen A. , Brockington Samuel F. , Timoneda Alfonso , Yim Won C. , Cushman John C. , Yang Ya
Published: October 2019

Gene tree discordance in large genomic datasets can be caused by evolutionary processes such as incomplete lineage sorting and hybridization, as well as model violation, and errors in data processing, orthology inference, and gene tree estimation. Species tree methods that identify and accommodate all sources of conflict are not available, but a combination of multiple approaches can help tease apart alternative sources of conflict. Here, using a phylotranscriptomic analysis in combination with reference genomes, we test a hypothesis of ancient hybridization events within the plant family Amaranthaceae s.l. that was previously supported by morphological, ecological, and Sanger-based molecular data. The dataset included seven genomes and 88 transcriptomes, 17 generated for this study. We examined gene-tree discordance using coalescent-based species trees and network inference, gene tree discordance analyses, site pattern tests of introgression, topology tests, synteny analyses, and simulations. We found that a combination of processes might have generated the high levels of gene tree discordance in the backbone of Amaranthaceae s.l. Furthermore, we found evidence that three consecutive short internal branches produce anomalous trees contributing to the discordance. Overall, our results suggest that Amaranthaceae s.l. might be a product of an ancient and rapid lineage diversification, and remains, and probably will remain, unresolved. This work highlights the potential problems of identifiability associated with the sources of gene tree discordance including, in particular, phylogenetic network methods. Our results also demonstrate the importance of thoroughly testing for multiple sources of conflict in phylogenomic analyses, especially in the context of ancient, rapid radiations. We provide several recommendations for exploring conflicting signals in such situations.
Evolution of the DAN gene family in vertebrates
Authors: Opazo Juan C. , Hoffmann Federico G. , Zavala Kattina , Edwards Scott V.
Published: October 2019

The DAN gene family (DAN, Differential screening-selected gene Aberrant in Neuroblastoma) is a group of genes that is expressed during development and plays fundamental roles in limb bud formation and digitation, kidney formation and morphogenesis and left-right axis specification. During adulthood the expression of these genes are associated with diseases, including cancer. Although most of the attention to this group of genes has been dedicated to understanding its role in physiology and development, its evolutionary history remains poorly understood. Thus, the goal of this study is to investigate the evolutionary history of the DAN gene family in vertebrates, with the objective of complementing the already abundant physiological information with an evolutionary context. Our results recovered the monophyly of all DAN gene family members and divide them into five main groups. In addition to the well-known DAN genes, our phylogenetic results revealed the presence of two new DAN gene lineages; one is only retained in cephalochordates, whereas the other one (GREM3) was only identified in cartilaginous fish, holostean fish, and coelacanth. According to the phyletic distribution of the genes, the ancestor of gnathostomes possessed a repertoire of eight DAN genes, and during the radiation of the group GREM1, GREM2, SOST, SOSTDC1, and NBL1 were retained in all major groups, whereas, GREM3, CER1, and DAND5 were differentially lost.
Genotype Concordance and Polygenic Risk Score Estimation across Consumer Genetic Testing Data
Authors: Batra Prag , Huang Kuan-lin
Published: October 2019

The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three major consumer services. We found low overlap among reported genotyped sites (2.7% across all three). While there was a high concordance between overlapping sites of the two SNP-array services (99.6%), there was a lower concordance between them and a low-pass whole-genome service (73.0%). Finally, we demonstrated that the discrepancy resulted in distinct APOE genotypes and genetic risk scores of Alzheimer’s disease determined using these data. Our results demonstrate genotype results across consumer genomics platforms may lead to different genetic risk estimates, highlighting the need for careful quality control and interpretation.
From cognitive control to creativity: The conflict resolution of surrealistic imagery
Authors: Ruzzoli Manuela , McGuinness Aoife , Morís Fernández Luis , Soto-Faraco Salvador
Published: October 2019

Surrealistic imagery juxtaposes common visual elements to create un-ordinary associations with semantically conflicting representations. We hypothesize that these images engage the conflict processing network that has been described in cognitive neuroscience theories, and probed with laboratory protocols such as the Stroop or Flanker tasks. We addressed this hypothesis by measuring mid-frontal Theta power using EEG while participants watched surrealistic images through a social media-like interface. Surrealistic images, compared to controls, produced a significant Theta power increase, as predicted from cognitive conflict theory. We also found increased memory for surrealistic images one week after exposure, compared to the controls. These findings provide evidence for the surrealistic artistic strategy to effectively engage viewer’ s cognitive control and boost memorability. In these studies, we provide validation of cognitive theories in real-life scenarios and insights regarding the use of neural correlates as effectiveness metrics in creative communication, as well as the arts.
Spatial variability in pollen and resource limitation for fruit production of two species in interior Alaska:Vaccinium uliginosumandV. vitis-idaea
Authors: Parkinson Lindsey Viann , Mulder Christa P.H.
Published: October 2019

Many recent studies assessing fruit productivity of plants in the boreal forest focus on interannual variability across a forested region, rather than on environmental variability within the forest. Frequency and severity of wildfires in the boreal forest affect soil moisture, canopy, and community structure at the landscape level, all of which may influence overall fruit production at a site directly (through resource availability) or indirectly (through impacts on pollinators). We evaluated how fruit production in two boreal shrubs,Vaccinium uliginosum(blueberry) andV. vitis-idaea(lingonberry), was explained by factors associated with resource availability (such as canopy cover and soil conditions) and pollen limitation (such as floral resources for pollinators and pollen deposition) across boreal forest sites of Interior Alaska. We classified our study sites into upland and lowland sites, which differed in elevation, soil moisture (lower in upland sites), and active layer (deeper in upland sites). We found that resource and pollen limitation differed between the two species and between uplands and lowlands. Lingonberry was more pollen limited than blueberry, and plants in lowland sites were more pollen limited relative to other sites while plants in upland sites were relatively more resource limited. Additionally, canopy cover had a significant negative effect in upland sites on a ramet’s investment in reproductive tissues and leaves versus structural growth, but little effect in lowland sites. These results point to importance of including pollinator abundance as well as resource availability in predictions for changes in berry abundance.
A new method of recording from the giant fiber of Drosophila melanogaster shows that the strength of its auditory inputs remains constant with age
Authors: Blagburn Jonathan M.
Published: October 2019

There have been relatively few studies of how central synapses age in adult Drosophila melanogaster. In this study we investigate the aging of the synaptic inputs to the Giant Fiber (GF) from the Johnston’s Organ neurons (JONs). In previously published experiments an indirect assay of this synaptic connection was used; here we describe a new, more direct assay, which allows reliable detection of the GF action potential in the neck connective, and long term recording of its responses to sound. Genetic ablation using diphtheria toxin expressed in the GF with R68A06-GAL4 was used to show that these signals indeed arose from the GF and not from other descending neurons. As before, the sound-evoked action potentials (SEPs) in the antennal nerve were recorded via an electrode inserted at the base of the antenna. We then used this technique to quantify the response of the JONs to a high frequency sound pulse, and also the strength of the JON-GF synapse, in males and female of different ages. At no age was there any significant difference between males and females, for any of the parameters measured. Sensitivity of the JONs increased between 1 d and 10 d, with the sound intensity that elicited a half-maximal SEP decreasing by 40%. This measure almost doubled by 20 d and had increased 3-fold by 50 d compared to 10 d. Thus, JONs are most responsive around the period when most matings are taking place. The strength of the JON-GF synaptic connection itself was quite variable and did not change significantly with age. As a result, the GF’s sensitivity to sound approximately followed the JONs’ sensitivity, but with greater variability.
Zinc-independent activation of Toll-like receptor 4 by S100A9
Authors: Loes Andrea N. , Shi Ran , Harms Michael J.
Published: October 2019

The homodimer formed by the protein S100A9 induces inflammation through Toll-like receptor 4 (TLR4), playing critical roles in both healthy and pathological innate immune responses. The molecular mechanism by which S100A9 activates TLR4 remains unknown. Previously, the interaction between purified S100A9 and TLR4 was shown to depend on Zn2+; however, the Zn2+ binding site(s) on S100A9 were not identified. Here, we investigated the role of Zn2+ binding in the pro-inflammatory activity of S100A9. We found that the S100A9 homodimer was prone to reversible, Zn2+-dependent aggregation in vitro. Using a combination of site-directed mutagenesis and Isothermal Titration Calorimetry (ITC), we identified multiple residues that contribute to Zn2+ binding in S100A9. We then used mutagenesis to construct a version of S100A9 with no detectable Zn2+ binding by either ITC or Inductively Coupled Plasma-Mass Spectrometry. This protein did not exhibit aggregation upon addition of saturating Zn2+. Further, despite the lack of Zn2+-binding, this protein was capable of activating TLR4 in a cell-based functional assay. We then modified the functional assay so the Zn2+ concentration was exceedingly low relative to the concentration of S100A9 added. Again, S100A9 was able to activate TLR4. This reveals that, despite the ability of S100A9 to bind Zn2+, S100A9 does not require Zn2+ to activate TLR4. Our work represents an important step in clarifying the nature of the interaction between S100A9 and TLR4.
FGFR1 is critical for Rbl2 loss-driven tumor development and requires PLCG1 activation for continued growth of small cell lung cancer
Authors: Kim Kee-Beom , Kim Youngchul , Kim Dong-Wook , Park Kwon-Sik
Published: October 2019

Small cell lung cancer (SCLC) remains a recalcitrant disease; limited therapeutic options have not improved overall survival and approved targeted therapies are lacking. Amplification of the tyrosine kinase receptor FGFR1 (fibroblast growth factor receptor 1) is one of the few actionable alterations found in SCLC genome. However, efforts to develop targeted therapies for FGFR1-amplified SCLC are hindered by critical gaps in knowledge around the molecular origins and mediator of FGFR1-driven signalling and the physiological impact of targeting FGFR1. Here we demonstrate the oncogenic impact of increased FGFR1 on the malignant progression of precancerous cells and the necessity of nonamplified FGFR1 for SCLC development and homeostasis. Unexpected dependency of Rbl2 loss-driven tumor development on FGFR1 in autochthonous mouse models reveals a novel function of p130 (encoded by Rbl2), a member of the RB family of tumor suppressors, as a regulator of FGFR1 expression. Additionally, FGFR1-dependent SCLC cells require activation of PLCG1 for continued growth. Together, this study uncovers mechanisms of FGFR1-driven SCLC that involves p130 upstream and PLCG1 downstream and provides potential biomarkers for anti-FGFR1 therapeutic strategy.