bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on the Long-Term Outcomes Following the Management of Incomplete Punctal Canalization
Authors: Saini Pragya , Bothra Nandini , Ali Mohammad Javed
Published: July 2021

Purpose:

To study the clinical profile, associated lacrimal disorders, and long-term outcomes following a membranotomy, in patients with incomplete punctal canalization (IPC).

Methods:

Retrospective interventional study was performed of all the patients diagnosed with IPC during the study period over 5 years from January 2015 to December 2020. The diagnosis of IPC was made based on the earlier published guidelines. A combination of rapid and slow taper Nettleship’s punctal dilators were used for an effective membranotomy, followed by further assessment of the lacrimal drainage passage. Appropriate interventions for associated lacrimal disorders were performed. Data collected on chart reviews include demographics, clinical presentation, laterality, type of IPC, associated lacrimal anomalies, management modalities, and long-term outcomes.

Results:

Ninety-eight puncta of 62 eyes of 46 patients with IPC were examined in the clinic. Incomplete punctal canalization-external membrane variant was seen in 62% (61/98) and internal membrane variant in 38% (37/98). Seventy-eight puncta (78/98, 79.5%) in 39 patients underwent membranotomy using Nettleship’s punctal dilator. Associated lacrimal drainage pathway deformities were seen in 31% of patients (12/39). Three puncta had mini-monoka insertion for associated canalicular stenosis and canalicular obstruction. Five patients with associated congenital nasolacrimal duct obstruction underwent probing, of which 3 patients needed dacryocystorhinostomy for complex congenital nasolacrimal duct obstruction. Associated punctal agenesis was noted in 3 patients involving the other punctum of the same eye. Canalicular wall hypoplasia involving 3 walls of the canaliculus was seen in 1 patient. At a mean follow up of 28 months, the anatomical and functional outcomes were noted in 100% and 97.4%, respectively.

Conclusions:

The long-term outcomes of membranotomy for IPC are excellent. Associated congenital lacrimal drainage anomalies are common with IPC.
Epibulbar Subconjunctival Apocrine Hidrocystoma
Authors: Charles Norman C. , Raju Leela V. , Kim Eleanore T.
Published: July 2021

Apocrine hidrocystomas are benign cystic tumors derived from apocrine sweat glands; they are most commonly located in the skin of the head and neck regions. Ophthalmic occurrences characteristically appear at the lash line and canthi of the eyelid, although rare instances have been described in the conjunctiva, caruncle, and orbit. The authors describe an exceptional instance of a mobile epibulbar subconjunctival apocrine hidrocystoma in a 57-year-old woman without a history of previous ocular injury or surgery. Histopathology of the excised specimen displayed an empty cyst lined by a double layer of cuboidal epithelium with the inner layer exhibiting periodic acid-Schiff-positive apical decapitation secretion. Confirmatory immunohistochemistry included reactivity with cytokeratin-7, smooth muscle actin, D2-40, and CDGFP-15.
Examination of the safety and effectiveness of low-concentration nitrous oxide anesthesia in cataract surgery
Authors: Noguchi Santaro , Nakakura Shunsuke , Noguchi Asuka , Nakama Sayuri , Aimi Miyuki , Kashima Tomoyuki , Tabuchi Hitoshi
Published: July 2021

Purpose:

To investigate the effects in cataract surgery using local anesthesia along with a 30% low-concentration nitrous oxide (N2O) anesthesia compared with local anesthesia only.

Setting:

Saneikai Tsukazaki Hospital.

Design:

Retrospective, consecutive study.

Methods:

Patients who underwent bilateral cataract surgery were enrolled. 37 patients using room air inhalation (Air group) and 45 patients using 30% low-concentration N2O anesthesia (70% oxygen, total 6 L/min) at surgery start (N2O group) were retrospectively reviewed. Systolic blood pressure (BPs), diastolic blood pressure (BPd), and heart rate (HR) at surgery start and end, and mean intraoperative oxygen saturation (% SpO2) were examined. Immediately following surgery, a questionnaire using the Visual Analog Scale score was done to determine intraoperative pain, anxiety, memory, and nausea.

Results:

No systemic symptoms in all patients and ocular complications requiring treatment were observed. For the N2O and air groups, changes in BPs were −5.38 ± 11.07(P = .01) and 1.27 ± 13.61 mm Hg, and HR were −2.24 ± 6.76 and 0.89 ± 5.18 bpm (P = .001), respectively; intraoperative SpO2 was 99.05% ± 0.74% and 97.44% ± 1.31% (P < .001), intraoperative anxiety was 21.76 ± 23.2 and 37.17 ± 32.79 (P = .002), and intraoperative memory was 55.24 ± 36.8 and 68.91 ± 33.81 (P = .01), respectively. No patients experienced intraoperative nausea. There was no statistically difference in BPd (P = .47) and intraoperative pain (P = .62).

Conclusions:

Low-concentration N2O anesthesia may not cause respiratory depression, abnormal vital signs, or nausea in cataract surgery. It can suppress intraoperative anxiety and memory and decrease and stabilize vital signs.
Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2021 ASCRS member survey
Authors: Chang David F. , Rhee Douglas J.
Published: July 2021

In an online survey of >1200 global cataract surgeons, 66% were using intracameral (IC) antibiotic prophylaxis. This compared with 50% and 30% in the 2014 and 2007 surveys, respectively. Irrigation bottle infusion and intravitreal injection was each used by only 5% of respondents. For IC antibiotics, vancomycin was used by 6% in the United States (52% in 2014), compared with 83% for moxifloxacin (31% in 2014). Equal numbers used compounded moxifloxacin or the Vigamox bottle as the source. There was a decrease in respondents using preoperative (73% from 85%) and postoperative (86% from 97%) topical antibiotic prophylaxis; the latter was not used by 24% of surgeons injecting IC antibiotics. Reasons cited by those not using IC antibiotics include mixing/compounding risk (66%) and being unconvinced of the need (48%). However, 80% believe having a commercially approved IC antibiotic is important; if reasonably priced, this would increase adoption of IC prophylaxis to 93%.
Deep learning for abdominal ultrasound: A computer-aided diagnostic system for the severity of fatty liver
Authors: Chou Tsung-Hsien , Yeh Hsing-Jung , Chang Chun-Chao , Tang Jui-Hsiang , Kao Wei-Yu , Su I-Chia , Li Chien-Hung , Chang Wei-Hao , Huang Chun-Kai , Sufriyana Herdiantri , Su Emily Chia-Yu
Published: July 2021

Background:

The prevalence of nonalcoholic fatty liver disease is increasing over time worldwide, with similar trends to those of diabetes and obesity. A liver biopsy, the gold standard of diagnosis, is not favored due to its invasiveness. Meanwhile, noninvasive evaluation methods of fatty liver are still either very expensive or demonstrate poor diagnostic performances, thus, limiting their applications. We developed neural network–based models to assess fatty liver and classify the severity using B-mode ultrasound (US) images.

Methods:

We followed standards for reporting of diagnostic accuracy guidelines to report this study. In this retrospective study, we utilized B-mode US images from a consecutive series of patients to develop four-class, two-class, and three-class diagnostic prediction models. The images were eligible if confirmed by at least two gastroenterologists. We compared pretrained convolutional neural network models, consisting of visual geometry group (VGG)19, ResNet-50 v2, MobileNet v2, Xception, and Inception v2. For validation, we utilized 20% of the dataset resulting in >100 images for each severity category.

Results:

There were 21,855 images from 2,070 patients classified as normal (N = 11,307), mild (N = 4,467), moderate (N = 3,155), or severe steatosis (N = 2,926). We used ResNet-50 v2 for the final model as the best ones. The areas under the receiver operating characteristic curves were 0.974 (mild steatosis vs others), 0.971 (moderate steatosis vs others), 0.981 (severe steatosis vs others), 0.985 (any severity vs normal), and 0.996 (moderate-to-severe steatosis/clinically abnormal vs normal-to-mild steatosis/clinically normal).

Conclusion:

Our deep learning models achieved comparable predictive performances to the most accurate, yet expensive, noninvasive diagnostic methods for fatty liver. Because of the discriminative ability, including for mild steatosis, significant impacts on clinical applications for fatty liver are expected. However, we need to overcome machine-dependent variation, motion artifacts, lacking of second confirmation from any other tools, and hospital-dependent regional bias.
Factors influencing locoregional recurrence and distant metastasis in Asian patients with cutaneous melanoma after surgery: A retrospective analysis in a tertiary hospital in Taiwan
Authors: Chu Po-Yu , Chen Yi-Fan , Li Cheng-Yuan , Yang Jai-Sing , King Yih-An , Chiu Yu-Jen , Ma Hsu
Published: July 2021

Background:

The goal of this study was to investigate the prognostic factors for locoregional recurrence and metastasis in patients with cutaneous melanoma (CM) who underwent surgery, especially in the acral lentiginous melanoma (ALM) subtype.

Methods:

This study was a retrospective review of patients who underwent surgery for CM at Taipei Veterans General Hospital between 2000 and 2018. We investigated the risk factors for locoregional and distant metastases. The association between clinicopathological factors and locoregional recurrence and distant metastasis of the CM and ALM subtypes was analyzed. In addition, the outcomes between the ALM and non-ALM groups were compared.

Results:

A total of 161 patients were included in the analysis. The most common histological subtype was ALM. The overall locoregional recurrence rate of CM was 13.0% and the distant metastasis rate was 42.9%, whereas that of the ALM subtype was 12.5% and 45.5%, respectively. In patients with CM, male sex, tumor with lymphovascular invasion, and positive lymph node status were the prognostic factors for both locoregional recurrence and distant metastasis. Among the patients with ALM, positive lymph node status was significantly associated with both locoregional recurrence and distant metastasis.

Conclusion:

In this cohort, factors influencing locoregional recurrence and distant metastasis were similar between the ALM and non-ALM groups. The above-recommended surgical margin did not show any benefit in either the CM or the ALM subtype. ALM can be handled using the same surgical strategy as CM in the Asian population.
The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19
Authors: Lai Yu-Ju , Chang Huan-Shuo , Yang Yi-Ping , Lin Tzu-Wei , Lai Wei-Yi , Lin Yi-Ying , Chang Cheng-Chang
Published: July 2021

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.
Loop Electrosurgical Excision Procedure in Managing Persistent Low-Grade Abnormality or Human Papillomavirus Positivity
Authors: Leung Shuk On Annie , Vitonis Allison F. , Feldman Sarah
Published: July 2021

Objectives

The aims of the study were to estimate the rate and to identify predictors of high-grade abnormalities among women with persistent low-grade abnormalities or high-risk human papillomavirus (hrHPV) positivity for at least 2 years stratified by presence (high risk) or absence (low risk) of previous high-grade results or HPV 16/18.

Materials and Methods

A retrospective cohort study of patients who underwent a loop electrosurgical excision procedure (LEEP) for persistent low-grade or hrHPV positivity was performed. Patients were stratified based on whether they had a history of high-grade and/or HPV 16/18 positivity. Rates of high-grade or worse abnormalities on LEEP were compared using Fisher exact tests. Logistic regression was used to evaluate the associations between patient characteristics and high-grade results on the LEEP.

Results

Three hundred eleven LEEPs were performed for persistent low-grade or hrHPV positivity. The rates of occult high grade were 12% and 22% among the low- and high-risk groups, respectively. Compared with those 45 years and older, the adjusted odds of high grade was 3.79 (95% CI = 1.19–12.1) for women aged 25–29 years. The odds of high grade was higher among current versus never smokers (6.40; 95% CI = 2.01–20.4) and those with a history of high-grade abnormality (2.23; 95% CI = 1.12–4.43). At 2 years, approximately half had an abnormal cytology and/or hrHPV positivity result independent of whether high grade was identified on their LEEP specimen.

Conclusions

Patients with persistent low-grade abnormalities or persistent hrHPV should be counseled on the risks and benefits of a LEEP given that 12%–22% have a risk of occult high grade, especially if they have a history of high-grade dysplasia.
A Retrospective Cross-sectional Study on the Risk Factors of Recurrent Falls Among Inpatients
Authors: Chang Wen-Pei , Jen Hsiu-Ju , Huang Tsai-Wei
Published: July 2021

Background:

Recurrent falls are more likely to cause injuries and disabilities than single falls.

Purpose:

This study investigated the incidence and risk factors of recurrent falls among inpatients.

Methods:

We analyzed inpatient fall data from the anomaly event notification database and electronic medical records of a hospital. We collected data regarding 1059 inpatients who had fallen during their hospital stay. Among these inpatients, 390 (36.83%) had fallen within the previous year.

Results:

Inpatients in the orthopedics and neurology wards were at a higher risk of recurrent falls than those in surgical wards; inpatients who were physically dependent were at a higher risk of recurrent falls than those who were physically independent; inpatients with poor vision were at a lower risk of recurrent falls than those without this issue; and inpatients who were using antidepressants were at a higher risk of recurrent falls than those who were not using antidepressants.

Conclusion:

The risk of recurrent falls is highly correlated with ward type, physical independence, self-perceived good vision, and use of antidepressants.
Validation of PROMIS-29 domain scores among adult burn survivors: A National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System Study
Authors: McMullen Kara , Bamer Alyssa , Ryan Colleen M. , Schneider Jeffrey C. , Gibran Nicole , Stewart Barclay T. , Mroz Tracy , Wolf Steven , Amtmann Dagmar
Published: July 2021

BACKGROUND

Patient-reported outcomes are important for understanding recovery after burn injury, benchmarking service delivery and measuring the impact of interventions. Patient-Reported Outcomes Measurement Information System (PROMIS)-29 domains have been validated for use among diverse populations though not among burn survivors. The purpose of this study was to examine validity and reliability of PROMIS-29 scores in this population.

METHODS

The PROMIS-29 scores of physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles, and pain interference were evaluated for validity and reliability in adult burn survivors. Unidimensionality, floor and ceiling effects, internal consistency, and reliability were examined. Differential item functioning was used to examine bias with respect to demographic and injury characteristics. Correlations with measures of related constructs (Community Integration Questionnaire, Satisfaction with Life Scale, Post-Traumatic Stress Checklist-Civilian, and Veteran’s Rand-12) and known-group differences were examined.

RESULTS

Eight hundred and seventy-six burn survivors with moderate to severe injury from 6 months to 20 years postburn provided responses on PROMIS-29 domains. Participants’ ages ranged from 18 years to 93 years at time of assessment; mean years since injury was 3.4. All PROMIS domain scores showed high internal consistency (Cronbach’s α = 0.87–0.97). There was a large ceiling effect on ability to participate in social roles (39.7%) and physical function (43.3%). One-factor confirmatory factor analyses supported unidimensionality (all comparative fit indices >0.95). We found no statistically significant bias (differential item functioning). Reliability was high (>0.9) across trait levels for all domains except sleep, which reached moderate reliability (>0.85). All known-group differences by demographic and clinical characteristics were in the hypothesized direction and magnitude except burn size categories.

CONCLUSION

The results provide strong evidence for reliability and validity of PROMIS-29 domain scores among adult burn survivors. Reliability of the extreme scores could be increased and the ceiling effects reduced by administering PROMIS-43, which includes six items per domain, or by administering by computerized adaptive testing.

LEVEL OF EVIDENCE

Diagnostic Test or Criteria, level III.
Breaching the curation bottleneck with human-machine reading symbiosis
Authors: Wong Cliff , Rao Rajesh , Yin Taofei , Statz Cara , Mockus Susan , Patterson Sara , Poon Hoifung
Published: July 2021

Purpose

The explosion of molecular biomarker and treatment information in the precision medicine era drastically exacerbated difficulty in identifying patient-relevant knowledge for clinical researchers and practitioners. Curated knowledgebases, such as the JAX Clinical Knowledgebase (CKB) are tools to organize and display knowledge in a readily accessible format; however, curators face the same challenges in comprehensively identifying clinically relevant information for curation. Natural language processing (NLP) has emerged as a promising direction for accelerating manual curation, but prior applications were often conceived as stand-alone efforts to automate curation, and the scope is often limited to simple entity and relation extraction. In this paper, we study the alternative paradigm of assisted curation and identify key desiderata to scale up knowledge curation with human-computer symbiosis.

Methods

We chose precision oncology for a case study and introduced self-supervised machine reading, which can automatically generate noisy training examples from unlabeled text. We developed a curation user interface (UI) for precision oncology and through iterative “curathons” (curation hackathons), conducted retrospective and prospective user studies for head-to-head comparison between manual and machine-assisted curation.

Results

Contrary to the prevailing assumption, we showed that high recall is more important for end-to-end assisted curation. In extensive user studies, we showed that assisted curation can double the curation speed and increase the number of findings by an order of magnitude for previously scarcely curated drugs.

Conclusion

We demonstrated that an iterative and thoughtful collaboration between professional curators and NLP researchers can facilitate rapid advances in assisted curation for precision medicine. Human-machine reading symbiosis can potentially be applicable to clinical care and research scenarios where curation is a major bottleneck.
Cooperative DNA base and shape recognition by the CCAAT-binding complex and its bZIP transcription factor HapX
Authors: Huber Eva M. , Hortschansky Peter , Scheven Mareike T. , Misslinger Matthias , Haas Hubertus , Brakhage Axel A. , Groll Michael
Published: July 2021

The heterotrimeric CCAAT-binding complex (CBC) is a master regulator of transcription. It specifically recognizes the CCAAT-box, a fundamental eukaryotic promoter element. Certain fungi, likeAspergilli, encode a fourth CBC-subunit, HapX, to fine-tune expression of genes involved in iron metabolism. Although being a basic region leucine zipper with its own DNA recognition motif, HapX function strictly relies on the CBC. We here report two crystal structures of the CBC-HapX complex bound to DNA duplexes with distinct sequence and position of HapX sites. In either structure, a HapX dimer targets the nucleic acid downstream of the CCAAT-box and the leash-like N-terminus of the distal HapX subunit interacts with CBC and DNA.In vitroandin vivoanalyses of HapX mutants support the structures, highlight the complex as an exceptional major and minor groove DNA binder, and enrich our understanding of the functional as well as structural plasticity of related complexes across species.
SnoRNA guide activities – real and ambiguous
Authors: Deryusheva Svetlana , Talross Gaëlle J.S. , Gall Joseph G.
Published: July 2021

In eukaryotes, rRNAs and spliceosomal snRNAs are heavily modified posttranscriptionally. Pseudouridylation and 2’-O-methylation are the most abundant types of RNA modifications. They are mediated by modification guide RNAs, also known as small nucleolar (sno)RNAs and small Cajal body-specific (sca)RNAs. We used yeast and vertebrate cells to test guide activities predicted for a number of snoRNAs, based on their regions of complementarity with rRNAs. We showed that human SNORA24 is a genuine guide RNA for 18S-Ψ609, despite some non-canonical base-pairing with its target. At the same time, we found quite a few snoRNAs that have the ability to base-pair with rRNAs and can induce predicted modifications in artificial substrate RNAs, but do not modify the same target sequence within endogenous rRNA molecules. Furthermore, certain fragments of rRNAs can be modified by the endogenous yeast modification machinery when inserted into an artificial backbone RNA, even though the same sequences are not modified in endogenous yeast rRNAs. In Xenopus cells a guide RNA generated from scaRNA, but not from snoRNA, could induce an additional pseudouridylation of U2 snRNA at position 60; both guide RNAs were equally active on a U2 snRNA-specific substrate in yeast cells. Thus, posttranscriptional modification of functionally important RNAs, such as rRNAs and snRNAs, is highly regulated and more complex than simply strong base-pairing between a guide RNA and substrate RNA. We discuss possible regulatory roles for these unexpected modifications.
Emergent evolutionary forces in spatial models of microbial growth in the human gut microbiota
Authors: Ghosh Olivia M. , Good Benjamin H.
Published: July 2021

The genetic composition of the gut microbiota is constantly reshaped by ecological and evolutionary forces. These strain-level dynamics can be challenging to understand because they emerge from complex spatial growth processes that take place within a host. Here we introduce a general population genetic framework to predict how stochastic evolutionary forces emerge from simple models of microbial growth in spatially extended environments like the intestinal lumen. Our framework shows how fluid flow and longitudinal variation in growth rate combine to shape the frequencies of genetic variants in sequenced fecal samples, yielding analytical expressions for the effective generation times, selection coefficients, and rates of genetic drift. We find that the emergent evolutionary dynamics can often be captured by well-mixed models that lack explicit spatial structure, even when there is substantial spatial variation in species-level composition. By applying these results to the human colon, we find that continuous fluid flow and simple forms of wall growth are unlikely to create sufficient bottlenecks to allow large fluctuations in mutant frequencies within a host. We also find that the effective gener-ation times may be significantly shorter than expected from traditional average growth rate estimates. Our results provide a starting point for qua ntifying genetic turnover in spatially extended settings like the gut microbiota, and may be relevant for other microbial ecosystems where unidirectional fluid flow plays an important role.
Repetition effects in action planning reflect effector- but not hemisphere-specific coding
Authors: Seegelke Christian , Schonard Carolin , Heed Tobias
Published: July 2021

Action choices are influenced by future and recent past action states. For example, when performing two actions in succession, response times (RT) to initiate the second action are reduced when the same hand is used. These findings suggest the existence of effector-specific processing for action planning. However, given that each hand is primarily controlled by the contralateral hemisphere, the RT benefit might actually reflect effector-independent, hemisphere-specific rather than effector-specific repetition effects. Here, participants performed two consecutive movements, each with a hand or a foot, in one of two directions. Direction was specified in an egocentric reference frame (inward, outward) or in an allocentric reference frame (left, right). Successive actions were initiated faster when the same limb (e.g., left hand - left hand), but not when the other limb of the same body side (e.g., left foot - left hand) executed the second action. The same-limb advantage was evident even when the two movements involved different directions, whether specified egocentrically or allocentrically. Corroborating evidence from computational modeling lends support to the claim that repetition effects in action planning reflect persistent changes in baseline activity within neural populations that encode effector-specific action plans.
Deforestation projections imply range-wide population decline for critically endangered Bornean orangutan
Authors: Voigt Maria , Kühl Hjalmar S. , Ancrenaz Marc , Gaveau David , Meijaard Erik , Santika Truly , Sherman Julie , Wich Serge A. , Wolf Florian , Struebig Matthew J. , Pereira Henrique M. , Rosa Isabel M.D.
Published: July 2021

Assessing where wildlife populations are at risk from future habitat loss is particularly important for land-use planning and avoiding biodiversity declines. Combining projections of future deforestation with species density information provides an improved way to anticipate such declines. Using the endemic and critically endangered Bornean orangutan (Pongo pygmaeus) as a case study we applied a spatio-temporally explicit deforestation model to forest loss data from 2001-2017 and projected future impacts on orangutans to the 2030s. Our projections point to continued deforestation across the island, amounting to a loss of forest habitat for 26,200 (CI: 19,500–34,000) orangutans. Populations currently persisting in forests gazetted for industrial timber and oil palm concessions, or unprotected forests outside of concessions, were projected to experience the worst losses within the next 15 years, amounting to 15,400 (CI: 12,000–20,500) individuals. Lowland forests with high orangutan densities in West and Central Kalimantan were also projected to be at high risk from deforestation, irrespective of land-use. In contrast, most protected areas and logging concessions currently harboring orangutans will continue to face low levels of deforestation. Our business-as-usual projections indicate the importance of protected areas, efforts to prevent the conversion of logged forests for the survival of highly vulnerable wildlife, and protecting orangutan habitat in plantation landscapes. The modeling framework could be expanded to other species with available density or occurrence data. Our findings highlight that species conservation should not only attempt to act on the current situation, but also be adapt to changes in drivers to be effective.
Left-handedness and its genetic influences are associated with structural asymmetries mapped across the cerebral cortex in 31,864 individuals
Authors: Sha Zhiqiang , Pepe Antonietta , Schijven Dick , Carrion Castillo Amaia , Roe James M. , Westerhausen René , Joliot Marc , Fisher Simon E. , Crivello Fabrice , Francks Clyde
Published: July 2021

Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We re-sampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers and right-handers showed average differences of surface area asymmetry within fusiform, anterior insular, anterior-middle-cingulate and precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2 and NME7 – the latter is mutated in left-right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas non-heritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.
Airborne environmental DNA for terrestrial vertebrate community monitoring
Authors: Lynggaard Christina , Bertelsen Mads Frost , Jensen Casper V. , Johnson Matthew S. , Guldberg Frøslev Tobias , Olsen Morten Tange , Bohmann Kristine
Published: July 2021

Assessing and studying the distribution, ecology, diversity and movements of species is key in understanding environmental and anthropogenic effects on natural ecosystems. Although environmental DNA is rapidly becoming the tool of choice to assess biodiversity 1–3 there are few eDNA sample types that effectively capture terrestrial vertebrate diversity and those that do can be laborious to collect, require special permits and contain PCR inhibitory substances, which can lead to detection failure. Thus there is an urgent need for novel environmental DNA approaches for efficient and cost-effective large-scale routine monitoring of terrestrial vertebrate diversity. Here we show that DNA metabarcoding of airborne environmental DNA filtered from air can be used to detect a wide range of local vertebrate taxa. We filtered air at three localities in Copenhagen Zoo, detecting mammal, bird, amphibian and reptile species present in the zoo or its immediate surroundings. Our study demonstrates that airDNA has the capacity to complement and extend existing terrestrial vertebrate monitoring methods and could form the cornerstone of programs to assess and monitor terrestrial communities, for example in future global next generation biomonitoring frameworks 4,5.
Beneficial Lactiplantibacillus plantarum promote Drosophila growth by down-regulating the expression of PGRP-SC1
Authors: Gallo Marialaura , Vento Justin M. , Joncour Pauline , Quagliariello Andrea , Maritan Elisa , Beisel Chase L. , Martino Maria Elena
Published: July 2021

Animals and their commensal bacteria are known to reciprocally influence many traits of their physiology. Specifically, microbes contribute to the maintenance of the immune system homeostasis, improve host digestive processes, and sustain host growth and development. Several studies have reported that such effects result from an intricate network of nutritional, metabolic and immune inputs and partly rely on the capacity of microbes to regulate the host’s transcriptional response. However, these evidences mainly come from comparing the transcriptional response caused by commensal bacteria with that of axenic animals, making it difficult to identify the specific animal genes that are regulated by beneficial microbes. Here, we employ a well-established model of nutritional symbiosis, Drosophila melanogaster associated with Lactiplantibacillus plantarum, to understand the host genetic pathways regulated by beneficial bacteria and leading to improved host growth and development. Using isogenic L. plantarum strains bearing different growth-promoting effects, we show that the microbial benefit to the host relies on the down-regulation of peptidoglycan- recognition proteins. In particular, we report that the lower expression of PGRP-SC1 exerted by growth-promoting bacteria is responsible for their higher proliferation and the consequent increased production of beneficial metabolites, which ultimately leads to improved host growth and development. Our study helps elucidate the mechanisms underlying the beneficial effect exerted by commensal bacteria, defining the role of PGRP-SC1 in the relationship between Drosophila and its gut microbes.

IMPORTANCE

Commensal bacteria are in constant association with their animal hosts, significantly affecting animal physiology through an intricate network of nutritional, metabolic and immune inputs. Yet, how beneficial bacteria specifically improve animal health is not fully understood. Here, we used a well-established model of nutritional symbiosis to understand how beneficial gut microbes improve host growth via regulation of its transcriptional response. Our study advances the current knowledge in host-microbe interactions by demonstrating that commensal bacteria improve fly growth by actively regulating the expression of immune effectors, which lead to higher immune tolerance. This leads to higher bacterial proliferation and the increased production of beneficial microbial metabolites, which are then consumed by the host. Our results shed light on the complex mechanisms underlying the relationships between a host and its gut microbes.
Exploring the human cerebral cortex using confocal microscopy
Authors: Pesce Luca , Laurino Annunziatina , Scardigli Marina , Yang Jiarui , Boas David A. , Hof Patrick R. , Destrieux Christophe , Costantini Irene , Pavone Francesco Saverio
Published: July 2021

Cover-all mapping of the distribution of neurons in the human brain would have a significant impact on the deep understanding of brain function. Therefore, complete knowledge of the structural organization of different human brain regions at the cellular level would allow understanding their role in the functions of specific neural networks. Recent advances in tissue clearing techniques have allowed important advances towards this goal. These methods use specific chemicals capable of dissolving lipids, making the tissue completely transparent by homogenizing the refractive index. However, labeling and clearing human brain samples is still challenging. Here, we present an approach to perform the cellular mapping of the human cerebral cortex coupling immunostaining with SWITCH/TDE clearing and confocal microscopy. A specific evaluation of the contributions of the autofluorescence signals generated from the tissue fixation is provided as well as an assessment of lipofuscin pigments interference. Our evaluation demonstrates the possibility of obtaining an efficient clearing and labeling process of parts of adult human brain slices, making it an excellent method for morphological classification and antibody validation of neuronal and non-neuronal markers.
Structural and functional analysis of lorlatinib analogs reveals roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer
Authors: Shiba-Ishii Aya , Johnson Ted W , Dagogo-Jack Ibiayi , Mino-Kenudson Mari , Johnson Theodore R , Wei Ping , Weinrich Scott L , McTigue Michele A , Walcott Makeba A , Nguyen-Phuong Linh , Dionne Kristin , Acker Adam , Kiedrowski Lesli , Do Andrew , Peterson Jennifer L , Barth Jaimie L , Yeap Beow Y , Gainor Justin F , Lin Jessica J , Yoda Satoshi , Hata Aaron N
Published: July 2021

The treatment approach to advanced, ALK-positive non-small cell lung cancer (NSCLC) utilizing sequential ALK tyrosine kinase inhibitors (TKIs) represents a paradigm of precision oncology. Lorlatinib is currently the most advanced, potent and selective ALK tyrosine kinase inhibitor (TKI) in the clinic. However, tumors invariably acquire resistance to lorlatinib, and after sequential ALK TKIs culminating with lorlatinib, diverse refractory compound ALK mutations can emerge. Here, we determine the spectrum of lorlatinib-resistant compound ALK mutations identified in patients after treatment with lorlatinib, the majority of which involve ALK G1202R or I1171N/S/T. By assessing a panel of lorlatinib analogs against compound ALK mutant in vitro and in vivo models, we identify structurally diverse lorlatinib analogs that harbor differential selective profiles against G1202R- versus I1171N/S/T-based compound ALK mutations. Structural analysis revealed that increased potency against compound mutations was achieved primarily through two different mechanisms of improved targeting of either G1202R- or I1171N/S/T-mutant kinases. Based on these results, we propose a classification of heterogenous ALK compound mutations designed to focus the development of distinct therapeutic strategies for precision targeting of compound resistance mutations following sequential TKIs.
Very Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation
Authors: Castell Anne-Laure , Vivoli Alexis , Tippetts Trevor S. , Frayne Isabelle Robillard , Moullé Valentine S. , Ruiz Matthieu , Ghislain Julien , Des Rosiers Christine , Holland William L. , Summers Scott A. , Poitout Vincent
Published: July 2021

Fatty-acid (FA) signaling contributes to β-cell mass expansion in the face of nutrient excess, but the underlying mechanisms are poorly understood. Here we tested the hypothesis that sphingolipids, generated by the intracellular metabolism of FA, are implicated in the β-cell proliferative response to FA. Isolated rat islets were exposed to individual FA in the presence of 16.7 mM glucose for 48 h and the contribution of the de novo sphingolipid synthesis pathway was tested using the serine palmitoyltransferase inhibitor myriocin, the sphingosine kinase (SphK) inhibitor SKI II, or adenovirus-mediated knockdown of SphK, fatty-acid-elongase-1 (ELOVL1) and acyl-CoA-binding protein (ACBP). Wistar rat were infused with glucose and the lipid emulsion ClinOleic and received SKI II by gavage. B-cell proliferation was assessed by immunochemistry or flow cytometry. Sphingolipidomic analyses were performed by LC-MS/MS. Amongst the various FA tested, only oleate increased β-cell proliferation. Myriocin, SKI II, and SphK knockdown all decreased oleate-induced β-cell proliferation. Oleate exposure did not increase the total amount of sphingolipids but led to a specific rise in 24:1 species. Knockdown of ACBP or ELOVL1 inhibited oleate-induced β-cell proliferation. We conclude that unsaturated very long-chain sphingolipids produced from the available pool of C24:1 acyl-CoA mediate oleate-induced β-cell proliferation in rats.
LGR6 is necessary for attaining peak bone mass and regulates osteogenesis through differential ligand use
Authors: Khedgikar Vikram , Charles Julia F. , Lehoczky Jessica A.
Published: July 2021

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a marker of osteoprogenitor cells and is dynamically expressed during in vitro osteodifferentation of mouse and human mesenchymal stem cells (MSCs). While the Lgr6 genomic locus has been associated with osteoporosis in human cohorts, the precise molecular function of LGR6 in osteogenesis and maintenance of bone mass are not yet known. In this study, we performed in vitro Lgr6 knockdown and overexpression experiments in murine osteoblastic cells and find decreased Lgr6 levels results in reduced osteoblast proliferation, differentiation, and mineralization. Consistent with these data, overexpression of Lgr6 in these cells leads to significantly increased proliferation and osteodifferentiation. To determine whether these findings are recapitulated in vivo, we performed microCT and ex vivo osteodifferentiation analyses using our newly generated CRISPR-Cas9 mediated Lgr6 mouse knockout allele (Lgr6-KO). We find that ex vivo osteodifferentiation of Lgr6-KO primary MSCs is significantly reduced, and 8 week-old Lgr6-KO mice have less trabecular bone mass as compared to Lgr6 wildtype controls, indicating that Lgr6 is necessary for normal osteogenesis and to attain peak bone mass. Toward mechanism, we analyzed in vitro signaling in the context of two LGR6 ligands, RSPO2 and MaR1. We find that RSPO2 stimulates LGR6-mediated WNT/β-catenin signaling whereas MaR1 stimulates LGR6-mediated cAMP activity, suggesting two ligand-dependent functions for LGR6 receptor signaling during osteogenesis. Collectively, this study reveals that Lgr6 is necessary for wildtype levels of proliferation and differentiation of osteoblasts, and achieving peak bone mass.
Genomic insights into the differentiated population admixture structure and demographic history of North East Asians
Authors: He Guanglin , Wang Mengge , Zou Xing , Tang Renkuan , Yeh Hui-Yuan , Wang Zheng , Yang Xiaomin , Xia Ziyang , Li Yingxiang , Guo Jianxin , Wang Rui , Liu Jing , Zhu Kongyang , Chen Jing , Yang Meiqing , Shen Qu , Chen Jinwen , Zhao Jing , Ma Hao , Wei Lan-Hai , Chen Ling , Liu Changhui , Liu Chao , Chen Gang , Hou Yiping , Wang Chuan-Chao
Published: July 2021

North China and South Siberia, mainly populated by Altaic-speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroad for the initial peopling of America and western-eastern trans-continental communication. Yet, the complex scenarios of genetic origin, population structure, and admixture history of North-East Asia remain to be fully characterized, especially for Mongolic people in China with a genome-wide perspective. Thus, we genotyped genome-wide SNPs for 510 individuals from 38 Chinese Mongolic, Tungusic, and Sinitic populations to explore the sharing alleles and haplotypes within the studied groups and following merged it with 3508 modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified significant substructures within Altaic-speaking populations with the primary common ancestry linked to the Neolithic northern East Asians: Western Turkic people harbored more western Eurasian ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed dominant Neolithic Mongolian Plateau (MP) or ARB ancestry; Southern Mongolic people in China owned obvious genetic impact from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians and the latter retained the dominant YRB and ARB Neolithic ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountain possessed a strong genetic affinity with Neolithic MP people, supporting the hypothesis of their eastern Eurasian origin and long-distance migration history. We also illuminated that historic pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to southern ones. We finally found natural signatures in Mongolians associated with alcohol metabolism. Generally, our results not only illuminated that complex population migration and admixture of Neolithic ancestral sources from the MP or ARB played an important role in the spread of Altaic-speaking populations and Proto-Altaic language, which partly supported the Northeast Asia-origin hypothesis, but also demonstrated that the observed multi-sources of genetic diversity contributed significantly to the modern existing extensive ethnolinguistic diversity in North-East Asia.
Choosing the Right Metrics for Listerine Brand Management in Brazil
Authors: Guissoni Leandro A. , Getulio Fundação , Faculty Adjunct , Farris Paul W. , Araújo Olegário , Vargas Fundação Getulio
Published: July 2021

Ronaldo Art, brand manager for J&J’s Listerine, reflected on the progress he had made in market penetration for the oral hygiene product from the time he started in the position in 2010 to late 2014. He wanted to develop a long-term strategy for the brand rather than stimulating short-term increases in market share, which could compromise the equity of the brand, its profitability, and its long-term competitive advantage. This case has been used in Darden’s second-year course “Marketing Metrics and Integrated Marketing Communications” and would work well in any course module focused on brand management and brand strategy.